Tetsuro's mother is murdered while the two of them travel through the snow by the villainous Count Mecha. Before she dies, Tetsuro's mother tells him to go to the planet Andromeda where he can get a machine body and not die like she did. Tetsuro passes out from the cold but is rescued by the mysterious Maetal, who gives him a pass to the Galaxy Express 999 for free under the condition that he will travel with her.

The 999's first stop is the planet Mars, a desolate planet where few live. When Tetsuro is provided a tour by a young woman, Freme, her boyfriend Geronimo shoots Tetsuro and steals his 999 pass.

Tetsuro meets Crystal Claire, a waitress on the 999 that is made entirely of glass. Claire's body was forced upon her by her mother and she is seeking to buy back her original body. Tetsuro finds his mother alive again on the train, but it is actually a monster that tries to pull him out of the train with it.The 999 arrives on the planet Titan, where Maetal is captured by machine men.

The bandit Antares sneaks aboard the 999 and starts stealing and killing people aboard. He meets Tetsuro and Maetel and forces the 999 to travel to his home by holding Tetsuro at gunpoint.

The 999 travels to Pluto, where the frozen human bodies of the machine people have been laid to rest. Tetsuro meets Shadow, the machine woman who is caretaker of the graves. Shadow shows him her frozen human body, a body so beautiful that she refused to have a face on her machine body since it couldn't compare to her human face. Shadow tries to capture Tetsuro to regain her human body, but Maetel saves him.

The 999 arrives at the Comet Library, where all the books published are located. There, a pair of men capture Tetsuro and try to force him into having a machine body.

The 999 falls into the Sargasso, where they find the remains of the 333, a missing train. Traveling aboard, Tetsuro, Maetel and the Conductor find only skeletons. A woman aboard the train, Ryuzu, reveals herself, saying that she sped up time on the train which killed everyone. Through her threats, she takes a hold of Tetsuro and departs the train's remains with him.

Ryuzu brings Tetsuro to her home. There she demands Tetsuro remain with her, showing him the skeletons of those who refused her. Ryuzu offers Tetsuro a machine body, then shows him her beautiful machine body. Ryuzu tells Tetsuro her sad past, of how she was emotionally blackmailed into getting this body by her lover, but then was cruelly abandoned by him when others copied her style.

The 999 made a stop on the planet Trader, a junction for different major rail lines. Tetsuro met a woman in destitute and decided to treat her for a meal. But this angered a mob of similarly impoverished people when he could not extend his generosity.

Hanako brought the still asleep Tetsuro to a neighboring planet aptly called Wildflower. They traveled to her home, and were greeted by her aging mother and ailing father. Without Tetsuro's knowledge (or consent), Hanako feigned their upcoming marriage, for which Hanako's parents were eager to prepare a banquet.

The 999 arrived at the formless world Naruba, where humans often traveled to end their lives. Two adolescent shape-shifting blobs kidnapped Tetsuro and Maetel and impersonated them for a chance to leave the planet.

The 999 arrives on a planet where the entire populace except for one person have been turned to stone by a petrification cloud. The one person still alive, a warrior, attacks Tetsuro and steals his pass, hoping to use it to escape and find a cure for his lover, who was turned to stone.

Additional people arrive on the planet who seek to steal the petrified remains of the warrior's lover. Moreover an another petrification cloud is approaching the planet.

The 999 arrives at the Dual Planets, a world full of machine people. When a large group of machine people at a restaurant treat Tetsuro and Maetel rudely, Tetsuro goes on a rampage and kills them all. Tetsuro and Maetel then meet Lala, a machine woman who steals Tetsuro's body, switching it with her own.

The 999 is pursued by the Black Knight, a caped figure in a dark, fog drenched world. The Black Knight requests Tetsuro stay on the planet and be his friend, but Tetsuro refuses and he attacks. They then travel to the planet Yonde 3 where the son of an innkeeper, a musician, desires Tetsuro's pass so he can leave the planet.

On their latest planet, Tetsuro meets Freiya, a poor girl who appears beautiful to him but is considered ugly and deformed by the other inhabitants of her planet because she does not glow in the dark with a uniform light. Freiya is an amateur animator who hopes to become a director someday.

The 999 arrives on a planet where everything is encased in armor, including a panzer beetle that severely wounds Maetel. Tetsuro travels the planet, searching for a doctor who can help her. The doctor however is too old to help, and his son, who is the only other person left alive on the planet tries to kill Tetsuro.

The 999 arrives on a planet containing a large mud pit that Maetel warns Tetsuro to not go near. When he does, Tetsuro is dragged into the pit and forced to live in a bubble with a woman who also calls herself Maetel.

The 999 made a two-week stop to the Planet of Confession, a world supposedly free of all evils. While the conductor decided to take his holidays on the planet, a robber appeared and took all of his money. The incident was made aware by the "Cleaningless Committee". Instead of catching the perpetrator, the committee decided to uphold the planet's reputation by trying to silence the three travelers.

The 999 travels to a planet full of professionals, and Maetel warns Tetsuro not to look anyone in the eye. When Tetsuro does so, he is captured by a professional hangman who tries to hang Tetsuro. Tetsuro is saved when another professional, a gunman arrives and shoots the hangman. This professional however insists on teaching Tetsuro to become a professional dueler.

The 999 arrives at a hollow planet with no gravity; as a result everything is a lot fatter looking, and can float through the air. Tetsuro and Maetel are confronted by cattle keepers but are able to escape. As they travel to their next planet Tetsuro meets an artist who has a wooden machine body. When they travel through a planet full of leaves, an electric mushroom threatens to destroy the train.

The 999 is attacked by the pirate ship Queen Emeraldes, which forces the train to a pirate planet. There Tetsuro and Maetel are captured by the pirate Emeraldes, a caped woman who desires Maetel's body.

The 999 arrives at the Battle Torn Planet, a planet that was split in two due to arguments over whether the planet should be scientifically advanced or primitive. Soon after disembarking, Tetsuro is kidnapped and Maetel is viewed as Queen by the planet's primitive occupants.

The 999 finds its next destination destroyed; it was demolished by a planet that travels through the dimensions, smashing other planets. When the 999 lands on this planet, they are confronted by the planet's ruler, Egoterina.

Tetsuro meets Clowmaria, a freedom fighter on a heavily industrialized world that is trying to get the people of her planet to change their ways.