The first thing Super Buu did after he transformed (aside from cracking his neck and powering up) was to brutally kill deranged gunman Smitty by going down his throat in liquid form and blowing him up. He didn't kill Hercule, as part of Majin Buu inside him remembered Hercule, so he went to Kami's Lookout (as he could now sense energy signals). He asked to fight Goten and Trunks, and after trying to stall him (during which time Super Buu did a Human Extinction Attack to kill all inhabitants of Earth except Hercule, Bee, Tien, Chiaotzu, and anyone at Kami's Lookout or Korin Tower), agreed to let him wait an hour before fighting them. During this time, Chi-Chi slapped him for killing Gohan and he turned her into an egg and crushed her.
Buu soon got impatient of waiting, so he got Piccolo to take him into the Hyperbolic Time Chamber where Goten and Trunks were training. Piccolo deliberately took the longest way possible to stall him before they reached the chamber and Goten and Trunks fused into Gotenks and fought Super Buu. Eventually Gotenks turned Super Saiyan and used Super Ghost Kamikaze Attacks on him to severely damage him, and even reduce him to molecules, but he was able to come back together. When Gotenks faked being unable to make any more ghosts, Piccolo destroyed the entrance to the chamber to trap them in.
In desperation, Buu yelled "LET ME OUT!", unwittingly using his Dimension Scream technique, (a technique where the user screams so loudly, they tear open holes between dimensions) to open a portal to the outside world, where he escaped to. He turned Krillin, Android 18, Marron, Yamcha, Puar, Oolong, Bulma, Videl, Master Roshi, Ox-King, and Mr. Popo into chocolate and ate them. When Gotenks turned Super Saiyan 3 and escaped, he fought Buu again, and was at a slight advantage until he lost his Super Saiyan 3 power and his fusion wore off. Gohan arrived shortly after, powered up by Elder Kai, and beat up Buu, who self-destructed in an attempt to kill Gohan. Buu survived and regenerated, and tricked Goten and Trunks into fusing again. He then absorbed Gotenks and Piccolo and transformed into a much more stronger and intelligent form. His antenna became a head tentacle.
Buu fought Gohan and gained the advantage, forcing Elder Kai to give Goku his life and give him fusion earrings to fuse with Gohan. Tien attacked Buu, and Goku arrived with the earrings, but Gohan lost his earring before he could put it on. Goku fought Buu, who lost most of his power as Gotenks's fusion wore off inside him. However, he turned his severed head tentacle into liquid and used it to absorb Gohan, drastically increasing his power into one of the most powerful villains in Dragon Ball Z.
Goku eventually fused with Vegeta to become Vegito and beat up Super Buu, with Buu's liquid form going down his throat ineffective, as well as his Super Ghost Kamikaze Attack, and even turning him into candy didn't stop him, forcing Buu to turn Vegito back. After taking several huge beatings (often being blown to bits or losing several limbs), Buu absorbed Vegito. This was Vegito's plan all along, as he wanted to rescue the others. After separating (due to Buu's stomach acid dissolving the fusion), Goku and Vegeta found Goten, Trunks, Piccolo, and Gohan absorbed, and cut them down from their cocoons (referred to by Buu as "people pods"). Returning to his original Super Buu form, he entered his own mind to fight Goku and Vegeta.
They could not destroy him inside his own head, and he nearly absorbed Vegeta at one point, but eventually Vegeta tore down the original Majin Buu. Instead of turning back into Evil Buu, however, he turned into Kid Buu.