Manuel also holds three world records as a member of a relay team, and she is a six-time individual NCAA Division I Women's Swimming and Diving Championships champion, becoming one of the first three African-American women to place in the top three spots in the 100-yard freestyle event in any Division I NCAA Swimming Championship.

She qualified for the 2013 World Aquatics Championships in Barcelona, and she won a gold medal in the preliminary for the 4×100-meter freestyle relay.

[1] She became one of the first three African-American women to place in the top three spots in the 100-yard freestyle event in any Division I NCAA Swimming Championship.

[1] She won a silver medal as part of the 4×100-meter freestyle relay along with Abbey Weitzeil, Dana Vollmer, and Katie Ledecky.

On the first day of the World Championships, Manuel anchored the women's 4×100-meter freestyle relay to a gold medal alongside Mallory Comerford, Kelsi Worrell, and Ledecky.

In similar fashion to the previous summer at the Olympics, Manuel upset the favorite by coming from behind to win the 100-meter freestyle with an American record time of 52.27, out touching Sjöström by just four-hundredths of a second.

[25] The day after, she won her fourth gold medal in the mixed 4×00-meter freestyle relay, where she split 52.18 on the anchoring leg.

The team of Kathleen Baker, King, Worrell, and Manuel broke the 2012 world record of 3:52.05 set by Missy Franklin, Rebecca Soni, Dana Vollmer, and Allison Schmitt.

[31][33] This was most won by any female in the sport of swimming at a single FINA World Aquatics Championships series meet conducted in long course meters.

[49][50] Manuel turned to full-time professional swimming in July 2018, forgoing her final collegiate season with Stanford.

The program teaches the life-saving skills of swimming and pool safety to young children from under-resourced communities often free of charge.

[55] Manuel signed a sponsorship with the popular swimwear company TYR Sport, Inc. in 2018 and entered the world of professional swimming.

The addition, often seen in the entertainment industry to require groups to reach a specific level of diversity, was a first ever agreement of its kind in professional sports.

[57] In TYR Sport, Inc.'s press release regarding the signing of Manuel, the company describes that the inclusion rider "ensures that [Simone's] partners [or TYR] extend meaningful opportunities to traditionally underrepresented groups and that diversity be reflected in the creative efforts [Simone] pursues with the brand".

[58] Although Manuel could not be physically present at the camp because she was training for the Olympics, she did visit the school earlier that year in March to introduce the summer program and have a meet and greet with the kids.