The UFC's top two heavyweights both arrived at the same place, however. They're headed for a third fight before the end of the year.
Velasquez knocked down Antonio "Bigfoot" Silva with a combination and finished him on the ground in the first round Saturday night, briskly defending his belt for the first time at UFC 160.
A few minutes earlier, former champion Dos Santos stopped Mark Hunt on a spinning kick to the head with 42 seconds left in the third round at the MGM Grand Garden.
With the preliminaries out of the way, Dos Santos and Velasquez are eager to meet in the third fight of their entertaining series. Each has beaten the other once, and UFC President Dana White plans to let them tangle again in the next six months.
"It's a no-brainer," White said. "If there was ever a trilogy, that's it right there."
Velasquez (12-1) made his first successful title defence with authority, rocking Silva in the opening minute before connecting with a right hand to Silva's chin and pummeling him on the ground until referee Mario Yamasaki stepped in.
"I want the best fights against the best guys, and this just comes with it," Velasquez said, indicating the championship belt around his waist. "The belt, keeping it, defending it, that's my main goal right now. Just happy with that."
Although Silva (18-5) was a heavy underdog, he was furious after Velasquez stopped him in the first round for the second straight year in the UFC's annual Memorial Day weekend show in its hometown.
Silva claimed Yamasaki had stopped the bout too quickly, and he insisted Velasquez hit him with "several illegal blows to the back of the neck."
"The ref came in, and he told me they had been connecting to the ear," Velasquez said. "It's all good."
There was no doubt about the finish by Dos Santos (16-2), who dispatched the tenacious Hunt with a risky, acrobatic kick in the final minute of a fight he appeared to be winning. Hunt was taken to a hospital after the bout, but Dos Santos left with respect for the New Zealand-born, Australia-based knockout artist.
"It was way harder than Cain's punch," Dos Santos said. "He has very heavy hands. I knew that. I respect him a lot, but I believe so much in myself and my striking skills. I believe I can knock anybody out."
Velasquez agreed that a third bout with Dos Santos "makes sense," and Dos Santos can't wait.
"I want that so bad," Dos Santos said. "Because, man, I really believe I can be the champion again, and I'll do my best to get there."
Earlier on the pay-per-view card, Brazilian light heavyweight Glover Teixeira (21-2) needed only 2:38 to submit James Te Huna with a guillotine choke for his 19th consecutive win, and Nova Scotia's T.J. Grant (21-5) earned the next shot at Benson Henderson's lightweight title with a dynamic first-round stoppage of Gray Maynard.
Although Velasquez didn't get much of a chance to show off his comprehensive skills against Silva, he still proved why he might be the first UFC heavyweight champion to stick around for a while.
The heavyweight belt has been historically difficult to defend, with champions winning only about 50 per cent of their fights while lower-weight champions such as Anderson Silva and Georges St. Pierre have reigned uninterrupted for years. Velasquez lost his first defence to Dos Santos, who defended the belt just once before Velasquez took it back.
Silva earned this unlikely title shot with two upset victories in the past year since his first fight with Velasquez, who battered him in a bloody first-round stoppage victory a year ago in the same arena.
Dos Santos hadn't fought since Velasquez reclaimed the belt with a comprehensive beating at UFC 155 in the same MGM Grand Garden cage. The fight left Dos Santos with a badly injured jaw and a discolored, swollen face requiring a few months to heal.
He had a difficult matchup against Hunt (9-8), who had won four straight fights after six consecutive losses to burnish his reputation as a fearsome puncher. He nearly didn't even make it to Las Vegas after getting into visa trouble while trying to leave Australia, apparently because of an old arrest.
Dos Santos and Hunt largely stayed on their feet, trading huge shots and showing off admirable chins in a crowd-pleasing display of striking. Dos Santos knocked down Hunt with an overhand right in the first round, but Hunt bounced right up and kept coming forward despite taking considerable punishment.
"Junior Dos Santos proved himself big-time tonight," White said. "I wondered what would happen if he stood in front of Mark Hunt and took those big shots. Much respect to Junior Dos Santos, he stood in there and exchanged punches."
Dos Santos likely had a comfortable lead on the scorecards against his bloodied opponent, but he kept trying for a knockout — even by unusual means. Moments after Dos Santos stunned Hunt with a left hand, he spun and launched a wheel kick that caught Hunt squarely on the top of the head, sending him backward in a heap.
Dos Santos pounced and landed one big punch before the fight was stopped. The former champion said he had never tried a spinning kick like that in a fight.
"I train that a lot in my gym," Dos Santos said. "All the time I train kicks. I never felt very confident to do that during the fights because normally my hands work. Tonight I saw the moment to throw the kick, and I did."
Velasquez's win was another impressive performance by the former Arizona State wrestler who won the heavyweight title with a first-round knockout of Brock Lesnar in October 2010. He lost the belt 13 months later to Dos Santos, getting stopped 64 seconds into his first title defence.
Velasquez's first fight back was against Silva, whose face was cut open by Velasquez's elbows in the opening minute. Silva survived just over 3 1/2 minutes, but left a sickening amount of blood on the canvas by the time Velasquez finished.
The rematch wasn't much more competitive, despite Silva's protests of an early stoppage.
Grant pulled a mild upset with his first-round win over Maynard, a longtime title contender coming off an 11-month layoff. Grant knocked Maynard backward with a big right hand and never let up, chasing the stumbling Maynard around the cage until the fight was stopped just 2:07 in.
"I've been working that exact combo, and it was just beautiful," Grant said. "I practiced that for like the last eight weeks straight, and it worked. ... Gray is not a guy I wanted to go to the ground with, and I saw he didn't move his feet too well, so I knew there were openings."
Grant has won five straight fights since moving to lightweight.
Earlier, lightweight Donald "Cowboy" Cerrone won every round in a bloody decision over K.J. Noons, the former Strikeforce fighter making his UFC debut. Cerrone earned his seventh win in nine UFC fights.