Krypto was the family dog in Jor-El's household, and was used for a test flight of the rocket that eventually carried baby Kal-El to Earth. However, Krypto's rocket was blown off course and drifted in space for many years until the rocket picked up the signal from Kal-El's rocket that landed on Earth. Krypto arrived when Kal-El was a teenager, and the two got along famously.
Krypto adventured alongside young Kal-El, though he was not publicly known. This new version of Krypto had superhuman (or, supercanine) abilities, but with a normal canine intellect. This initially caused a great deal of trouble for his new master. For instance, Krypto would scratch at a door to indicate he wanted to go out and unintentionally gouge big chunks out of the door with his super-strength or inflict grevious bodily harm when combating villains (since Krypto bites the way a regular canine would, only without being careful about his super-strength). As a result, Krypto was for some time locked away in the Fortress of Solitude under the care of one of Superman's robots programmed to emit the scent of the dog's real master. Superman has gone to great lengths to train the dog, and Krypto has occasionally accompanied the Man of Steel on missions. Batman never misses an opportunity to poke fun at Krypto when Batman and Superman don't see eye-to-eye.
Krypto had a surprisingly violent reaction to Kara Zor-El when he first encountered her. The dog happened upon the girl while she was exploring the Fortress of Solitude. Krypto attacked, going so far as to use his heat vision and other potentially lethal attacks.
Some time later, Superman left Krypto in Superboy's care, saying that Smallville's open spaces were a better place for the dog, and that Superboy could use a friend. Their relationship had a shaky start, not helped by Krypto getting Superboy in trouble with the superheroine Starfire for destroying her alien garden.
However, they slowly developed a close friendship in which Krypto willingly did anything he could to protect Conner. One example of this loyalty was Krypto's quick defense of Conner from an outraged Superboy-Prime. Although Krypto was injured, this only strengthened his relationship with Conner.
With the murder of Conner by Superboy-Prime during the Infinite Crisis, Krypto has been taken by Superman to his retreat at the Fortress of Solitude where the sole remaining Earth-made Superman Robot now called "Ned" watches over and plays with Krypto.
Krypto was left with Martha Kent in the wake of Jon Kent's death, and is playing around in Smallville with Conner Kent in the wake of his resurrection. Most recently, Krypto joins Superman and Conner in a battle against the Black Lantern Superman (Kal-L). The battle sheds insight into Krypto's emotions in-battle, where he is awash with love, rage and will.