LAS VEGAS — Amid a sea of roars for the Brazilian mixed martial artist Amanda Nunes, a fan of her challenger, Julianna Peña, made sure to cheer loudly despite being outnumbered on Saturday night.

“Go, Peña,” the fan exclaimed as the arena lights dimmed. “You can do it.”

Peña’s disadvantage in loyalists reflected the circumstances she faced. Across from her stood Nunes, considered the greatest female fighter in the history of the Ultimate Fighting Championship and in mixed martial arts in general. Opening odds in the U.F.C. 269 event made her an enormous betting favorite to retain her bantamweight title — one of her two belts.

But as Nunes walked to the cage, Peña, an American, danced playfully to the music. The commentator Daniel Cormier, a retired fighter, said on the pay-per-view broadcast that he thought Peña was nervous because of her facial expression and back-and-forth pacing.

As the saying goes, looks can be deceiving.

Peña (12-4-0) orchestrated an upset of Nunes (21-5-0), completing it by crawling onto the champion’s back in the second round and forcing her into submission with a rear naked choke. In the headliner, Charles Oliveira of Brazil (32-8-0) successfully defended his lightweight belt, also via a rear naked choke, beating the No. 1 contender, Dustin Poirier of the United States (28-7-0).

Peña’s win was an exclamation point along the winding path her career has taken, and it put a question mark on Nunes’s. Such is the risk of combat sports.

“I got nothing to prove,” Peña said. “Everybody was sleeping on me, and I shook up the world.”

Peña, 32, withstood early pressure from Nunes. In the beginning of the second round, Peña’s face still looked serious while Nunes was smiling slightly. That soon changed. Both fighters began throwing punches, and the tempo escalated. Peña connected cleanly with a couple of left jabs to Nunes’s face, then landed an overhand right. Nunes grappled with her as a last-ditch defense and retreated toward the fence. Peña slung her to the mat and completed the choke.

“I just, today, checked out,” Nunes told Joe Rogan, the podcast host and U.F.C. commentator, inside the octagon afterward.

As Peña lay on top of Nunes, she said later in a news conference, she was unaware of how much time remained in the round. Moments later, the referee stopped the fight and threw her off her defeated opponent. Once she realized what had happened, she climbed up the cage railing and screamed.

“Julianna is a person who always believed in herself and believed that she could win this fight if she got it,” the U.F.C. president, Dana White, said at the news conference. “It’s one of the things that makes this sport so incredible.”

Rarely has anyone dominated Nunes, 33, in quite this way since she entered the U.F.C. in 2013. Her rise included easily dispatching Miesha Tate, Ronda Rousey, Holly Holm and Cris Justino, known as Cyborg. They were all pillars of women’s mixed martial arts and helped accelerate its footprint. Her defeat of Justino in 2018 to earn the featherweight title made her the first woman in U.F.C. history to hold two belts at once.

But Peña, who entered the promotion in 2013, had wanted to to fight Nunes for five years, ever since the night Nunes beat Tate to become champion at U.F.C. 200 in 2016. Peña claims Nunes avoided her and chose different opponents each time, saying their brawl would be an unfavorable stylistic matchup. The two were scheduled to fight in August, but Nunes contracted the coronavirus, forcing the fight’s delay. It frustrated Peña, and in one instance she mimicked a reporter at a news conference and asked White when the two would finally compete.

Peña’s coronation on Saturday is the next chapter in her up-and-down journey. While training in 2014, she tore the anterior cruciate ligament, medial collateral ligament, lateral collateral ligament and meniscus in her right knee. The recovery process forced her to sit out for over a year. She also did not fight in 2018 because of the birth of her daughter.

“Nothing was going to stop me from getting this belt,” Peña said. “This has been 13 years grinding, and it’s finally come to fruition. And it’s my time.”

The outcome, though, complicated the U.F.C.’s plans for a hypothetical blockbuster. Had Nunes won, her next fight would most likely have been against Kayla Harrison, a champion in the Professional Fighters League. Harrison’s league contract expired in October. White said in a phone interview last week that he and other U.F.C. officials met with Harrison on Thursday night.

Nunes, who was not made available to reporters afterward, still has options. A rematch is most likely, but she could also defend her featherweight belt. The first openly lesbian U.F.C. champion, Nunes recently married her partner, and they had a baby last year; White said it would not be surprising if Nunes stopped fighting.

“She has a lot of money and she has a baby now, a family — these things change you,” White said.

Peña’s victory capped a successful year for the U.F.C. The company in April became the first sports league to operate an event at full capacity amid the coronavirus pandemic. The eight pay-per-view shows with spectators sold out, White said, including Saturday’s. U.F.C. 269 generated $8 million in ticket sales, the largest gate amount, White said, for a U.F.C. show at T-Mobile Arena in Las Vegas that did not feature the brash Irishman Conor McGregor.

White, in the phone interview, said he hoped coronavirus restrictions would ease in 2022 so the promotion could host fights outside the United States, including in England, France and Africa.

High-profile stars could also return. McGregor, who lost to Poirier in July after landing awkwardly and breaking his left tibia, announced on social media that he could begin sparring around April. White said he was unsure whom his next opponent would be, but it will not be Olivera. Poirier won the first round on Saturday night with his striking, but Olivera smothered him in the second with strong jujitsu. In the third, he latched on to Poirier’s back and choked him while standing.

White said that Justin Gaethje would fight Oliveira next and that he would assess McGregor’s future when the fighter was healed.

“The one thing I don’t want him to do is rush it,” White said. “Take his time, and if that timeline is true, then he’ll fight this summer.”

White said Jon Jones, the former light heavyweight champion, should also fight in 2022. Jones, who was charged with misdemeanor battery domestic violence in September in Las Vegas, had been preparing to transition to heavyweight and is likely to fight the winner of the bout in January between Francis Ngannou and Ciryl Gane.

For now, though, White said he was focusing on celebrating 2021, including with a staff holiday party on Sunday.

“It’s the first one we’ve had in two years,” he said. “I’m going to wreck this whole crew.”