In 2011, dos Santos won the UFC title from Velasquez in 64 seconds, knocking him out with a right hand to the head in a bout in which both men were fighting with very badly injured knees.
Last year, Velasquez turned the tables and regained the belt, pummeling dos Santos over five rounds in a stunningly one-sided match.
There was little drama, suspense or sustained two-way action in either of them.
Yet the third fight is on the way, and everyone seems to be excited about it.
"No brainer," UFC president Dana White said of a third Velasquez-dos Santos match after both men won by highlight-reel knockouts in the co-main and main events before 11,089 at UFC 160 at the MGM Grand Garden. "If ever there was a trilogy, that's it right there."
Dos Santos earned his spot with a rousing win over Mark Hunt in which he could never take a breath because the threat of a Hunt knockout was so real every second of the bout. But as the fight was winding down, dos Santos caught Hunt with a left hook to begin the closing sequence.
Hunt has one of the best chins in the sport and didn't go down, but he was clearly hurt. Dos Santos missed a jab, but then quickly spun and landed a wheel kick to the head that dropped Hunt. Dos Santos landed a shot from the top before referee Steve Mazzagatti quickly stopped it.
It was a move dos Santos had never tried in competition previously.
"I trained that [kick] a lot in my gym, all the time," dos Santos said. "I train kicks in the gym, but I train everything: Wrestling, jiu-jitsu, Muay Thai. I never felt very confident to do that during a fight. Normally, my hands work. Tonight, I saw the moment to throw the kick, and I did, and it brought me to victory."
The hands were what worked for Velasquez on Saturday. An All-American wrestler before turning pro, Velasquez has spent countless hours working on his striking at the American Kickboxing Academy in San Jose, Calif., with coach Javier Mendez.
On Saturday, the fruit of his labor was evident. He caught Antonio "Bigfoot" Silva with a beautiful right hand that came behind a solid jab and dropped the massive Brazilian. Velasquez quickly ended it with ground and pound, forcing referee Mario Yamasaki to stop it at 1:21 of the first.
Silva complained that Velasquez hit him with illegal blows on the back of the neck, and he sat at the post-fight news conference with an ice pack on it.
Velasquez, though, wasn't buying it.
"The ref came in [to the dressing room before the fight], and he told me that anything to the ear was all good, so that's what I tried to do," Velasquez said calmly.
The finish guaranteed a third fight between them, much to dos Santos' delight. He was beaming the moment his fight with Hunt ended and the grin didn't leave his face throughout the news conference.
The build-up will be massive – it always is for a title fight between a champion and a former champion who also happen to be the two best men in the division – but it could also be a setup up for a major letdown.
There wasn't anything compelling in either of those first two fights. White, though, began the sales pitch from the podium at the news conference on Saturday.
"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. I actually thought Junior would come out and shoot and take this thing to the ground right away. Much respect to Junior dos Santos. He stood in the pocket, he stood in there and exchanged big punches. He has an unbelievable chin and unbelievable power.
"Cain has proven himself. People have questioned Cain's chin, because of the first Junior fight and that Cheick Kongo fight. Cain has an awesome chin. And in that second fight, I didn't think Cain would stand up with Junior, and he did and hurt him with punches. This is what I'm talking about. When you talk about a trilogy between two heavyweights, this is a trilogy."
Each of them has delivered many brilliant moments in the cage during their careers, but despite five-plus rounds with each other, they haven't put together that memorable battle against each other.
Typically, Velasquez was low key and said only, "That fight makes sense. I'm all up for that fight."
Dos Santos, though, was thrilled to have another shot at the belt. He said he wants to fight until he's in his mid-to-late 40s and dreams of making a series of title fights.
To him, there is no better way to start than against the man who may ultimately define his career.
"My next fight is for the title and that's what I want," he said. "I believe so much I can stay on top of the division for a long time, and I'll do my best to get there."
It's always great whenever the best fight the best.
Hopefully, a fight for the ages between them isn't too much to ask.