Goku's friend Krillin is murdered by one of King Piccolo's sons, Tambourine. Attempting to avenge his friend, he is defeated by Tambourine, because he was still weak from his fight with Tien, but a fully recovered Goku kills him easily in a later confrontation. An enraged King Piccolo almost kills Goku, After recovering from his defeat, he seeks out the Ultra Divine Water, which could unlock his powers or kill him. Surviving the Water, he travels to the castle of King Furry, where he kills another of Piccolo's sons and challenges the King himself to a fight. The pair have a drawn-out and bitter fight that leaves both horribly wounded. Ultimately, Goku manages to kill Piccolo by punching through his chest. With his dying breath Piccolo spits out an egg that contains his reincarnation, Piccolo Jr. Unaware of this, Goku begins to search for a possible way to revive the dragon Shenron. This leads him to the Guardian of Earth, Kami, and ultimately to the resurrection of all the friends who had been killed by Piccolo. Goku then begins training with Kami and Mr Popo in order to prepare for the 23rd World Martial Arts Tournament. Despite suffering extreme injuries, Goku defeats Piccolo in the final round, becoming the winner of the tournament. Goku and Chi-chi, a young woman he had met while travelling, get married. 

Now living with his wife and young son, Gohan, Goku's life is interrupted by the arrival of Raditz, his long-lost brother. Raditz informs him of his Saiyan heritage, as well as telling him that he was meant to take over the Earth. Refusing to carry out this mission, Goku is attacked by Raditz, who kidnaps Gohan and instructs him to kill a hundred humans or have his son murdered. Goku joins forces with Piccolo, and together with the help of Gohan they defeat Raditz, though Goku also dies. Traveling through the Other World, Goku begins training for the imminent arrival of more Saiyans. His friends wish him back to life, but it takes him sometime to arrive, and by the time he does many of his friends have been killed by the Saiyans, Vegeta and Nappa. Goku easily defeats Nappa, and manages to defeat Vegeta after a protracted battle. He chooses to spare the injured Vegeta's life after the battle. 

Severely injured, Goku spends some time in hospital before being completely healed by a Senzu Bean. Goku then travels to the planet Namek where his friends are searching for the Namekian Dragon Balls. There, he engages in battles with members of the Ginyu Force, the elite fighters of the villainous Frieza. He manages to defeat many of them, but is seriously wounded after a quarrel with their leader due to a special attack which enabled the user to exchange bodies with victims. He retreats to be healed, and in the meantime Frieza arrives and attacks Goku's friends. He returns to find the battle turning against his friends. Enraged by the death of Krillin, Goku transforms into his Super Saiyan form, which turns the tide of the battle in his favor. Ultimately, he defeats Frieza. He leaves the planet in a Ginyu Force ship, which takes him to the planet Yardrat. His friends back on Earth believe him to be dead, but later learn he is alive when they attempt to resurrect him. He declines to return to Earth and remains on Yardrat for some time more, learning the skill of Instant Transmission while there.

Returning to Earth after two years, Goku encounters Trunks, the son of Bulma and Vegeta from the future. The boy warns him about future events, and provides him with a cure for a virus he will contract in the near future. At this time a new villain rises, named Cell. Goku, Gohan, Vegeta and Trunks travel to the Hyperbolic Time Chamber to undergo intense training; there, Gohan is revealed to be potentially more powerful than Goku. They emerge from the chamber and Goku begins preparing to battle Cell, as well as getting a new Guardian of Earth, Dende, to create new Dragon Balls so that he can set right what Cell has put wrong. At the Cell Games, Goku battles Cell at full strength, but finds himself unable to defeat his opponent. He cedes the match, trusting Gohan to defeat Cell. Gohan does so, and Cell attempts to self-destruct and destroy the planet as revenge. Goku steps in and transports both of them to King Kai's planet , resulting in both his and Cell's deaths as well as King Kai's. Cell manages to resurrect himself, and Goku, trapped in the Other World, encourages Gohan to fight him. After Cell is finally completely destroyed, Goku insists he be allowed to remain dead, since he believes that all the troubles on Earth were caused due to him .

He returns to Earth for a brief period seven years later to participate in the 25th World Martial Arts Tournament. There, he meets his youngest son, Goten, and becomes embroiled in defeating the evil wizard Babidi, who orchestrates the theft of Gohan's Super Saiyan energy. They attack Babidi's ship, and Babidi possesses Vegeta, then sets Vegeta and Goku to fighting one another. The pair fight for some time before Goku attempts to halt the fight so that they can team up to defeat Babidi's monster, Majin Buu. He is knocked unconscious by Vegeta, who then abandons him. He seeks healing from Dende and teleports all his friends to himself, teaching Trunks and Goten how to perform the Fusion Dance, which will combine them into a far more powerful being. Goku then fights Majin Buu, using his powerful Super Saiyan 3 form. He easily holds his own against the monster, but does not defeat it. The strain of maintaining the form forces him to return to the Other World. There, he observes the fight between Majin Buu and the newly-created Gotenks via a crystal globe. Gotenks performs well, but is ultimately unable to defeat the monster and is absorbed into it, as is Gohan. Goku is returned to Earth and He and Vegeta fuse to become Vegito, easily defeating the monster. Vegito allows itself to be absorbed into the monster to rescue its friends and family. After a brief battle, it succeeds and Vegeta and Goku return to their normal bodies. Kid Buu destroys the planet, briefly killing most inhabitants, but they are soon restored. Goku fights Kid Buu, and gathers energy from most sentient beings around him (using the Genki Dama Technique) to destroy Kid Buu.