The 27-year-old finished with a combined score of 119.750 after competing in the uneven bars, floor exercise, balance beam, and vault.
The seven-time Olympic medalist and gymnastics veteran had one stumble during the vault, while attempting her eponymous trick known as the "Biles."
But she quickly shrugged it off, saying "I'm not mad," referring to her performance.
She was still able to cruise to the top spot on the podium, with her closest competitor Skye Blakely 5.900 points back in second. Kayla DiCello came in third.
Biles has continued to battle back after withdrawing from some events during the Tokyo Olympic Games in 2021, citing struggles with her emotional health.
"It was hard after Tokyo -- just to trust myself," she said in a press conference following her win.