Strickland came into the bout on the back of two wins, while Adesanya was making the first defence of his second title reign after emphatically beating long-term rival Alex Pereira in April.
Adesanya, competing in his 11th title fight, oozed confidence as he walked briskly to the octagon.
But, following an uneventful start to the first round, the odds started to even out as Strickland dropped Adesanya with a clean right hand, sparking the contest into life.
The champion recovered to reach the end of the round, but in knocking down Adesanya, Strickland laid down a marker that many of Adesanya's former opponents had failed to set.
Adesanya started to land more consistently in the second round, peppering the challenger with leg kicks, but Strickland, as he would for the remaining rounds, continued to be the aggressor.
And despite consistently pushing forward against a slick counter-striker in Adesanya, Strickland was able to avoid the majority of the champion's retaliations.
Halfway through the bout, Strickland's corner sensed their fighter could be on course for victory, asking for more urgency, adding "we didn't come all this way to lose a decision".
Strickland continued to press for the remainder of the fight, using his jab effectively, with Adesanya on the back foot and unable to inflict any meaningful damage in response.
As the fight ended, Strickland raised his arms in celebration, confident of victory, while a dejected-looking Adesanya walked over to his corner.
After the judges announced Strickland as the winner, Adesanya embraced the emotional American, before raising his hand in victory.
It meant Strickland won his maiden UFC title in his first championship bout, recording the 28th win of his 33-fight career.
"Izzy's had how many highlight knockouts, he's beaten the majority of my friends pretty easily. I was even doubting myself at times, but the fans in Australia motivated me," said Strickland.
"I give so many brain cells to the MMA gods every day. I thought I'd be walking away a little bloody and broken up, I'm still shocked that didn't happen, this is the first time I'm lost for words.
"But remember, this gold around my waist doesn't mean [anything]. What matters is how you live your life, and I'm living better through you guys, for you guys, thank you."
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