Manuel not only gave Team USA its first gold medal in that competition in decades, the win marked various firsts for her as well. Here are 5 things to know about the American gold medalist:
When Manuel and her Canadian counterpart came to the wall at the same instant, they set a new Olympic record of 57.20 seconds in that event.
"My first gold medal, at my first Olympics, is kind of a surprise to me," Manuel told reporters. "I never thought I would be in this position but I'm so blessed and honored to be on the medal stand."
She set an American record, too
And while she was toppling Olympic records, the 20-year-old set yet another mark.
Manuel became the first African-American woman to win a gold medal in an individual swimming event for the United States.
"It means a lot [to be the first black woman to earn gold in the pool]," Manuel said after the race. "This medal is not just for me. It's for a whole bunch of people that came before me and have been an inspiration to me. And it's for all the people after me, who believe they can't do it."
Even as she celebrated her triumph, she also acknowledged the recent shootings of black men by police officers in the US.
"It means a lot, especially with what is going on in the world today, some of the issues of police brutality," Manuel said, according to USA Today. "This win hopefully brings hope and change to some of the issues that are going on. My color just comes with the territory."
With the win, she also gave the US its first gold in the women's 100 free since 1984 -- when Nancy Hogshead and Carrie Steinseifer tied. That race was the second, and only other time, there has been a tie in an Olympic swimming event.
Manuel also has a silver medal to her name. She helped the US women's team to second in the 4x100m freestyle race.
She attends Stanford for a reason
Manuel grew up in Texas, but decided to go west for college. She is a rising junior at Stanford University in California, where she's part of the swimming team. She said she picked the university for its values.
"You have to work hard and be pretty smart to get into a school like this -- but honestly, that's another reason why I picked it, because I wanted to be in this atmosphere and challenge myself," she told USA Swimming this year.
"It challenges me academically and athletically, and socially I get to be around such different people, though we also have something in common by being here," Manuel told USA Swimming about attending Stanford.
And she's in good company. Her roommate in Rio, Katie Ledecky, is a fellow gold medal winner and an incoming freshman at Stanford.
She started swimming at age 4
USA Swimming described Manuel as a "powerful and gutsy no-limits swimmer." But her path to get here has been a long one.
Manuel's parents put her in swimming lessons at age 4 so she'd learn how to be safe in water, she said this year. But she enjoyed it so much, she immersed herself fully by age 9.
She told CNN in March that she at times struggled with being African-American in a sport typically dominated by white athletes.
"I see other blacks and African-Americans doing basketball, and running and doing volleyball, so I think the hardest part was coming to terms with, you know, this is what you love to do so you should do it," she said.
During her senior year in high school, she rose to prominence in the swim community when she broke the national record for her age group on her 17th birthday.
"Her 50 free swim was the fastest 17-18-year-old time and the second-fastest American time in history," USA Swimming said.
Manuel's passion for the sport extends beyond the pool. She also served on USA Swimming's diversity and inclusion committee, which, she told CNN, helped her overcome some of the loneliness she felt at being one of the few minorities in the sport.
"I met other minorities who were facing some of the same things that I was, so through that process I didn't feel so alone," she said in March.
Her brothers keep her competitive
As the youngest sibling and the only girl, Manuel has spent her lifetime sharpening her competitive streak.
"I am fortunate that I have two older brothers and they have definitely helped me with being competitive just to keep up with them," she told USA Swimming.
"We were always encouraged to try what we wanted to do. As long as we tried our hardest and did the best we could, it didn't matter what we did," she said.
Her brothers chose a different yet equally competitive sport: basketball.