The former UFC bantamweight champion was dethroned after being rocked by a straight left before being dropped unceremoniously on her backside after a perfectly-timed head kick from former boxer Holm before the end of the second round.
It ranks right up there with plucky Matt Serra's stunning TKO victory against Georges St-Pierre back in 2007 which shocked the mixed martial arts industry to its core.
At the time, Rousey was considered virtually untouchable, a dominant force to be reckoned with in a bantamweight division where she had blown everyone away in impressive fashion.
But 'The Preacher's Daughter' completely ripped up the script, leaving her reputation lying in tatters.
Albuquerque-based 40-year-old Holm was a 20-1 'dog to dethrone former 135lbs champ Rousey - but she somehow managed to pull off what many had deemed was the impossible.
Speaking after the fight, Holm said: “I’m trying to take it in, but it’s crazy.
"Getting in here, I had so much love and support. I felt like, how can I not do this with all that love. I had the best coaching, from stand-up to grappling to wrestling.
“Everything that we worked on presented itself in the fight. I haven’t spent this much time in the gym in my life. Everything we worked on happened tonight.”
WATCH: Ronda Rousey suffers first UFC loss to Holly Holm
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Some UFC fans took to Twitter to react to the iconic KO six years later, as one person wrote: "One of the greatest upsets not just in all of MMA but also in all of combat sports history."
Another fan chimed in: "Always blame her coaches for ruining her. Was never a stand up fighter but her ground game was unmatched. Could’ve beat everyone if she played to get strengths. Still the [goat emoji]."
While a third added: "Ronda wasn’t the same again after that night."
Rousey herself spoke about how she struggled to get over her emphatic loss to Holm.
“Honestly, my thought I was like, in the medical room and I was down in the corner,” Rousey told Ellen DeGeneres.
“I was sitting in the corner [thinking] like, ‘What am I anymore if I’m not this?’
"And I was literally sitting there and thinking about killing myself and that exact second, I’m [thinking] ‘I’m nothing, what do I do anymore, and no one gives a s--- about me anymore without this.’”News Now - Sport News