On the first night of the swimming portion at the Olympics, she won a silver medal as part of the 4×100-meter freestyle relay along with Manuel, Dana Vollmer, and Katie Ledecky in 3:31.89, which was a new American Record. Her split of 52.56 was the fastest among her team. She also swam in the preliminary heats of the 4x100-meter medley relay and received a gold medal when the team won in the finals. In her individual events, Weitzeil finished seventh in the 100-meter freestyle with a time of 53.30 and missed qualifying for the final of the 50-meter freestyle.