"You know, sweetheart, if there's one thing I've learned, it's this: nobody knows what's gonna happen at the end of the line, so you might as well enjoy the trip."
— Manny's last words to Meche before leaving the Land of the Dead.
Manuel Calavera, as well as being the protagonist, is the only playable character in Grim Fandango (except when driving the Bone Wagon). The player assumes the role of Manny at the beginning of Year One, following right up to his departure from the Land of the Dead at the end of Year Four. As penance for his sins, Manny is not allowed to simply leave the Land of the Dead, but instead must work as a travel agent (a.k.a. a Reaper) in the Department of Death. He spends the first two years of the game following Meche.
Manny is shown to be incredibly sarcastic and quick-witted all through his journey across the eighth underworld. At the start of the game, he is portrayed as rather pessimistic to his fate. As the game goes on, he becomes significantly more optimistic and sometimes heroic, prompting the attention of various revolutionary characters, such as Salvador Limones.
One of Manny's very noticeable traits is his competitive streak. As a salesman, he constantly compares himself to Domino and, later, as a club owner to Maximino. Early on in the game, he wonders whether or not he would be happier working a ship, but dismisses it as he knows he'd be too competitive and not rest until he was captain.
While not always a bad thing, Manny's competitive streak often blinds him to the needs of others early on in the game. For instance, he first saw Meche as his ticket out of the ninth underworld, but later he became more sensitive to other trapped souls and chose to help them too.
Manny seems to like playing card games too, mainly solitaire, as he owns a deck that's frayed around the edges.
He is presumed to be a Mexican-American, due to his name and his fluency on speaking the Spanish language.
Almost nothing is known about Manny's life in the Land of the Living (although a non-canonical reference suggests he was a dead pirate). Periodically throughout the game, Manny states he doesn't know what sin he committed that got him stuck at the Department of Death— he may in all fairness have committed an innocent sin— but if so he, is willing to work his time off regardless. In Year One, he says that he has no one he cares to visit during the Day of the Dead festival, suggesting he may have no family or friends, or at least none he wishes to see.
During his time at the Department of Death, it is known he has spent several years working there, and in his early days made several premium sales, including sports cars, cruises, and top of the line Double N tickets. It was during this time he came to understand the behavior of Double N tickets and how they physically fly to their appointed soul. He is also known to have logged more significant time at the D.O.D than even his boss, Don Copal.
Manny used to have Domino Hurley's office, but he was somehow demoted to the storage room, which became his office. Whether this is because of the scams his superiors were running is unknown, but given Manny's nature to figure things out quickly and his competitiveness, it's a possibility.
The game opens in the city of El Marrow, where D.O.D. travel agent Manuel Calavera works. He is first seen welcoming Celso Flores, newly dead, to the Land of the Dead. Manny explains that each immigrant soul must embark on a journey, which normally takes four years— unless that soul had been very good in life and deserves a better way to travel. However, Manny finds that Celso does not qualify for any travel package. Celso is then forced to travel on foot with The Excelsior— a walking stick with a compass in the handle. Celso takes his situation in stride, stating that at least he isn't stuck like Manny is.
After returning to the office, Manny receives a special service order: a mass poisoning has occurred in the Land of the Living, and there are too many dead to assign customers. Manny takes advantage of what seems like the perfect opportunity to get a good client. However, Domino Hurley, Manny's business rival and coworker, had given Manny's driver the day off, preventing him from getting a good client. Manny then goes to the garage and meets Glottis, a mechanic demon. He hires Glottis as his new driver, though it was already too late— by the time Manny had arrived in the Land of the Living, there was only one dead body left: Bruno Martinez, a snotty soul.
Tired of getting bad clients, Manny decides to steal one of Domino's clients: Mercedes "Meche" Colomar. He is convinced that Meche deserves a Double N Ticket because she was a very kind person, dedicating her time to the most needed. To Manny's surprise, his office computer concludes that Meche deserves nothing. He leaves his office and is suddenly called by Don Copal, his boss. After an argument between employer and employee, Don Copal asks his secretary, Eva, to call Meche in— only to discover that she had already left, saying "[she] had a long walk ahead". Manny is fired and locked in Glottis's room in the garage. Some time passes, and a stranger offers to unlock the door, if only Manny would swear loyalty to the D.O.D., which Manny refuses to do, even after being asked several times. Convinced of Manny's will, the man reveals himself to be Salvador "Sal" Limones, and invites Manny to join the Lost Souls Alliance, a revolutionary organization of which he is founder.
Within the LSA hideout, Manny learns that there is a web of corruption within the DOD, Meche being one out of many others cheated out of their Double-N tickets. Part of the scam is automatically saddling innocent agents like Manny with bad clients and outright rigging his computer to have all his clients receive nothing, no matter how good they were. Like Manny, Sal was once a reaper himself. Eva is also shown to be an LSA agent. After running some errands for Sal, he helps Manny get out of El Marrow, following an underground passage that opens at the edge of the Petrified Forest. Venturing within, Manny finds an unemployed and devastated Glottis, who literally reaches into his chest and throws his heart away from grief. After Manny finds and returns Glottis's heart, the two travel through the Petrified Forest unhindered before encountering the demon beavers, which Manny defeats with the use of a fire extinguisher.
After getting out of the Forest, the pair reach Rubacava. Searching for Meche, Manny wanders into the dense fog, only to fall off the end of a terrace and into the water below. He is saved by a sailor named Velasco. After being saved, Manny goes to a restaurant and finds Celso, who is working as a janitor. Celso explains that he is waiting for his wife, saying that Manny would be free to take his job as soon as his wife arrived. Manny tries to help look for Celso's wife, though he learns through Velasco that she left Rubacava two months prior, in the arms of another man. Upon learning this, Celso decides to look for his wife himself, leaving Manny with the job. The year ends with a reflection of Celso: Manny mopping the floor, waiting for Meche.
A year later, Rubacava has grown, and Manny is now the owner of the renamed restaurant Calavera Café, which is also a nightclub and a casino. Manny is first seen smoking on the roof, when his employee, Lupe, appears and tells him that a client is looking for him. Manny dismisses her, but a persistent Lupe wins the argument. Manny goes to see the client, who looks suspiciously like Meche. The strange person is revealed to be a demon raven, and upon being approached, flies away. Manny uses the on-terrace binoculars and sees Meche being manhandled by Domino onto a cruise ship. Manny tries to give chase, though loses his grip when Meche throws a bottle at him. Manny is once again saved by Velasco. Manny learns that the ship is headed to Puerto Zapato, and that the Limbo is the only ship that goes that far. In order for Manny to get onto the ship, he needs to do three things: get tools for Glottis, obtain membership to the Sea-Bee Union, and take the place of Seaman Naranja, the only sailor yet to report for duty.
Manny talks with Terry, an unemployed Sea-Bee, and learns that Terry doesn't have his tools anymore: he had to sell them to feed his family and tries to live honestly, but barely manages. Manny convinces him to rebel against the oppression, but Terry is seen by Chief Bogen and is arrested. Manny looks for Nick Virago, Maximino's lawyer in the Blue Casket, Olivia Ofrenda's nightclub and a place for beatniks. There, he finds Lola, a photographer who is trying to prove that Olivia is not good for Max, takes a photo of Nick and Olivia kissing each other and runs away. She manages to hide the photo and leave clues, but Nick sprouts her before Manny could get there. Following the clues, Manny finds the photo and blackmails Nick to free Terry. Terry retrieves his tools back and protests against the tiranny. Manny asks Glottis to carry them when they leave town.
Criminal Chowchilla Charlie promises a Union Card if Manny retrieves some stolen money from Max. Using a VIP Pass, Manny enters the High Rollers Lounge. He locks Raoul inside the pantry and waits for Glottis to drink all the wine, then hides in the empty cask to get into the cellar. Using a forklift to stop the elevator, Manny discovers a secret room and finds Charlie's suitcase. To Manny' surprise, there isn't money inside, but instead hundreds of Double N tickets. He hands over the suitcase to Charlie at gunpoint and receives the Union Card.
To stop Naranja from boarding the Limbo, Manny goes to Toto Santos's place where Naranja is getting a scrimshaw treatment. Using a turkey baster filled with hookah water from the Blue Casket, which he mixes with his beer, Manny makes Naranja fall asleep. Then, he takes Naranja's dog tags and goes to the morgue. There, he throws the dog tags in one of the corpses, making both Velasco and the coroner Membrillo believe that Naranja was sprouted.
After doing this, Manny closes his own nightclub by making Chief Bogen lose at the roulette tables. Bogen starts a blitz in the place and Glottis is kicked out from the High Rollers Lounge. They get aboard the Limbo and the year ends with Manny cleaning the floor.
In the third year, Manny is captain of the former Limbo ship (re-named Lola after his sprouted friend) along with Glottis, who has heavily modified the ship to be able to move at great speed. Upon his arrival at Puerto Zapata, a carrier pigeon from Salvador informs Manny that Meche never made it that far, but threw herself overboard at The Pearl. At the same time, men working for Hector LeMans invade the ship disguised as customs officials and sprout the ship's crew. Glottis manages to save Manny from the boarders, and with clever use of the anchors, they're able to escape before finally sinking in what remains of their ship.
Under the ocean they meet a strange little fellow named Chepito, who tells them he's been walking the ocean floor for years, and that a strange glow in the distance is "The Moon". At once, Manny suspects it's The Pearl, and with Glottis' help, they make their way over to find an octopus who snatches souls who have fallen overboard and takes them captive in a submarine to sail away to a small outcrop island at the Edge of the World. Here, they are used as slave workers to mine coral for making light bulbs as a cover operation.
Manny and Glottis arrive at the underwater facility and meet Domino, who runs the operation and has been keeping Meche captive. Domino drops Glottis over the Edge and puts Manny in charge of two child workers named Pugsy and Bibi Peligiano, who are kept in a cage and forced to make light bulbs. Manny has to free Meche from a cell and escape with Glottis and the other imprisoned souls on the ancient S.S. Lamancha, after rescuing it from the Edge. They are stopped by Domino, who has a brief stand-off with Manny on his submarine before being shredded by the Lamancha's crushers.
After travelling for a year through snowy wastelands, Manny, Meche, Glottis, and the other freed souls arrive at the site of a large Mayan-style temple. The long journey has left Glottis very ill and weak, as he has gone for too long without driving. The temple is a gateway to the ninth underworld— the Land of Eternal Rest. It is guarded by the mysterious Gate Keeper, who keeps everyone but Manny, Meche and Glottis in a waiting room, waiting for their tickets. Manny manages to help find a fuel for a vehicle built by Glottis-like mechanic demons, and it takes them all the way back to Rubacava in order to pick up the Bone Wagon. Manny also meets Olivia again, who comes along with them. In their old vehicle, the groups travels back to El Marrow, which has been taken over by Hector LeMans and is now called Nuevo Marrow.
Manny, Meche, and Glottis return to the headquarters of the L.S.A., which has expanded throughout Nuevo Marrow's sewers. Manny disguises himself with "Johnny Thunder" stage makeup and Chowchilla Charlie's suit, and heads up into Hector LeMans's casino equipped with a loading Sproutella gun. He reveals himself to Hector and tries to sprout him, but he is distracted by Hector's bird, and Hector escapes with a suitcase full of Double N tickets.
Outside of the train station, Manny gets into a car with Olivia, who reveals herself as Hector's girlfriend and accomplice and drives Manny to Hector's private greenhouse. Manny is forced to enter the greenhouse and is shot by a gloating Hector LeMans. However, he uses liquid nitrogen to save himself, and picks up Salvador's gun and ammo after Sal sacrifices himself to sprout Olivia. Manny finishes Hector off by firing Sproutella into the greenhouse water supply.
After the demise of LeMans, Manny and everyone he helped is seen on the Double N train heading back to the Mayan temple. Manny says his goodbyes to Glottis, who is sad to see his friend go but happy with his new life. Manny and Meche are finally united as they ride into the ninth underworld on the Number Nine.
"My scythe; I like to keep it next to where my heart used to be." —Examining his scythe
"They say black is slimming." —To Glottis, on his new job as a driver
"My name is Manny Calavera. I'm your new travel agent." —To customers
"Ay Chihuahua!" —When in trouble
"Ah, the old files, the old clients, the glory days when people died with dignity and Domino Hurley didn't exist." —Examining a filing cabinet at the D.O.D
"Oh man, did I come in on Saturday again?" —To Eva
"It's my boss's secretary's evil twin!" —Seeing Eva in the L.S.A
Manny Calavera made a cameo appearance in another Lucasarts game "The Curse Of Monkey Island", in which he sat quietly in captain Blondebeard's chicken restauraunt until Guybrush pushed him for attention and a badge fell off the skeleton reading "Ask Me About Grim Fandango".