In the co-main event, challenger Cody Garbrandt scored a thrilling unanimous decision victory over Dominick Cruz in another stunning upset to claim the men's bantamweight belt.
Brazil's Nunes lit up the former champion from the off, rocking Rousey with a flurry of big punches, her superior boxing never allowing the Californian to close the gap and use her judo skills to take the fight to the floor.
Stunned early on, Rousey had no answer to the power of the 28-year-old and referee Herb Dean quickly stepped in to stop the fight as Rousey was stung again and could no longer defend herself.
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"She did a lot for the sport – she was the champion, but now I am the champion," said an elated Nunes in the Octagon following her victory.
Rousey left the Octagon immediately following the official decision, making no comment to the press.
The defeat could signal the end of the road for the 29-year-old Californian, who lost her title a little over a year ago when she was knocked out in stunning fashion by Holly Holm's head kick in the main event at UFC 193 in Melbourne.
Holm then lost to Miesha Tate in her first defence in March, and Tate did little better, turning over the belt to Nunes at UFC 200 in July.
Rousey, a judo bronze medallist at the 2008 Olympics, may be one of the biggest draws in the UFC, but she is not universally popular, and the fact that she was allowed to shun the media in the run-up to this fight was not well-received by fighters or fans.
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But no-one can argue with her previous record as the first female bantamweight champion in the UFC and her six successful defences of her title before succumbing to Holm. Her stature as one of the biggest draws in mixed martial arts saw her get a $3 million purse for Friday's fight, plus an undisclosed share of the pay-per-view revenues.
In contrast, Nunes was paid $100,000 to show and another $100,000 as a win bonus for her first title defence, apart from an undisclosed share of pay per view revenues.
Nunes walked away with something much more valuable – the women's bantamweight belt, and the chance to start a new chapter in the history of mixed martial arts.
In the co-main event, Grabrandt scored a huge upset, sending Cruz crashing to the canvas three times in the fourth round before winning on the judges' scorecards. Cruz, until now the first and only champion in the history of the UFC's bantamweight division, can have no complaints after being out-thought and out-fought over five gruelling rounds that featured plenty of trash talk between the two fighters.
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