Manuel competed for the first time since anchoring the United States to a relay bronze medal, shaking off a five-day layoff to post the 11th-fastest time in the preliminaries of the 50-meter freestyle at 24.65 seconds.
The frenzied dash from one end of the pool to the other is the American swimmer's only individual event in Tokyo. She was among 16 swimmers advancing to Saturday's semifinals.
"It kind of felt like another first swim," Manuel said. "First swims are always a little rocky. I'll kind of reset and get ready for tomorrow morning."
After being diagnosed with overtraining syndrome, Manuel shockingly failed to qualify for the 100 freestyle -- the event she won at the 2016 Rio Games to become the first Black American to capture an individual gold in swimming.
Manuel was silver medalist in the 50 five years ago, but she'll have to overcome some tough competition to get back to the medal podium.
Australia's Emma McKeon, who won the 100 free during the morning session, set an Olympic record in the 50 heats at 24.02, eclipsing the mark set at the 2012 London Games by Ranomi Kromowidjojo of the Netherlands.
"I think I always have a chance," Manuel said. "If I'm diving in the water and I'm on the heat sheets, I still have opportunity to win the race. So I think it's important that I continue to believe in myself."
Manuel had not competed since Sunday, when the Americans earned bronze in the 4x100 free relay with her taking the final leg.
"It's been a while that I haven't had such a jam-packed schedule," she said. "But I'm just trying to rest as much as possible, continue to cheer on Team USA, but still focus on the races that I have, especially since they're at the end of the meet."
Caeleb Dressel has been busier of late.
After setting an Olympic record in the semifinals of the 100 butterfly during the morning session, he returned to the pool to post the top time in the preliminaries of the 50 free.
The American star touched in 21.32 to lead the field heading into Saturday's semifinals.