Schmitt was born in Pittsburgh, Pennsylvania in 1990 to Ralph and Gail Schmitt. Raised as one of five siblings in what is still her hometown of Canton, Michigan, Schmitt's father is a financial analyst and her mother is a system project manager. Schmitt considers her parents have been the most influential and helpful people in her life. "They are so supportive of my dreams and ambitions," she said in 2008, adding, "they have given me so many opportunities to excel in life and have set a good example for me to follow."
She started swimming at age nine, saying she followed her older sister, Kirsten, into it. "I thought about quitting," Schmitt said, "but stayed one more season and loved it." Prior to settling on swimming, she said she tried soccer, dance, basketball, volleyball, softball; and though she said she had the equipment for hockey, she decided to swim instead.
From ages 11 through 14, Schmitt swam with the Ann Arbor Swim Club (AASC) in Ann Arbor, Michigan (which, in 2006, merged into Club Wolverine). In an interview during the 2012 Summer Olympics, Josh Morgan, her then-AASC coach, said there was no indication in those years just how fast she would one day become. He said she started to show real potential, later, in the spring of her junior year in high school when she went to a 2007 Junior National Team competition. Calling it "her first real breakout swim," he said she went "from pretty fast to really fast," dropping four to five seconds off her 200-meter freestyle short course time of normally around a minute fifty-two seconds, down to around a minute forty-seven, thereby putting Schmitt in what Morgan called "elite company."
Schmitt went to Canton High School in Canton Township, Michigan, from which she graduated in the spring of 2008. During her senior year, as she continued to swim at what had, by then, become Club Wolverine on the University of Michigan campus in nearby Ann Arbor, she began training alongside Olympian Michael Phelps under the guidance of Phelps's long-time coach, Michigan Wolverines head coach Bob Bowman. Before the Summer Olympics in Beijing, having ended his tenure at University of Michigan, Bowman moved to Baltimore in anticipation of being named the head coach and CEO of the prestigious North Baltimore Aquatic Club the following September. Both Phelps and Schmitt followed, with Schmitt moving to Baltimore just after her spring 2008 high school graduation in order to train full-time with Phelps and Bowman during the weeks leading-up to the 2008 Olympics (at which Schmitt won her first Olympic medal, a bronze in the 4×200-meter freestyle relay).
After the Summer Olympics, in the fall of 2008, Schmitt moved to Athens to become a freshman at the University of Georgia, majoring in psychology, and minoring in childhood and family development. She joined coach Jack Bauerle's Georgia Bulldogs swimming and diving team, after she had just swum in the Summer Olympics under Bauerle in his capacity as the games' women's swimming head coach. She participated in NCAA competition during her freshman, sophomore and junior years, ultimately becoming a four-time NCAA national champion by winning the 500-yard freestyle in 2009, 2010, and 2011, and the 200-yard freestyle in 2010. While at college in Athens, Schmitt also became involved in Athens Bulldog Swim Club (ABSC) competitions on the University of Georgia campus.
During her first three years at the university, she trained with Phelps and Bowman in Baltimore only during summers, between semesters. However, in preparation for the 2012 Summer Olympics in London, she took the 2011–2012 school year (her senior year) off, and so did not compete with the Bulldogs that year; and, instead, she moved to Baltimore and trained full-time with Bowman and Phelps at the NBAC; which training consisted of at least four hours in the pool and one hour on dry land, every day, six days a week.
After the 2012 Summer Olympics, Schmitt returned to the University of Georgia to complete her senior year of college, She was the recipient of the Honda Sports Award for Swimming and Diving, recognizing her as the outstanding college female swimmer of 2012–13. Following her return from London, Schmitt started suffering from depression, finding the increased public attention to be overwhelming. Her anguish led to bad swimming results, leading her to not qualify for various international competitions. After opening up her feelings to Phelps and Bowman in January 2015, Schmitt decided to attend therapy sessions in secret to her family. Once Schmitt's cousin April Bocian committed suicide on May, she opted to reveal herself to her family and also make her emotional issues public, feeling it would help others in the same situation. She has since been training under Bowman at Arizona State University, hoping to get in shape for a possible third Olympic appearance at the 2016 Summer Olympics.
Schmitt wrote on the bio form for her USA Swimming organization membership that she enjoys scrapbooking, photography, playing outdoor games and board games; and that her ultimate way to relax is watching a movie or getting a massage. Whenever she returns home to Canton she likes to visit the local youth swim clubs and high school swim teams, both swimming and talking with the young swimmers, and encouraging them as a role model and mentor. "I love motivating these kids when they’re just starting to pave their own paths in life," she said.
About it all, Schmitt has said: "I didn't start swimming competitively until I was 10 and didn't really focus on it until I was 12, yet it's such a huge part of my life and I can't imagine my life without it. It's been an amazing journey, but more than that, it's shaped who I am as a person. The best part is all the friends I have made. I believe that I literally have the best friends anyone could ever imagine hoping for, and I met almost all of them because of swimming. Taking in all the memories with these amazing people, I feel pretty lucky with the paths I have crossed, and the people I have met because of swimming."
At the 2009 World Championships in Rome, Schmitt competed in three events, the 200-meter and 400-meter freestyle, and the 4×200-meter freestyle relay. In her first event, the 400-meter freestyle, Schmitt recorded the second best time in the heats with a time of 4:02.80. However, in the final she placed 4th with a time of 4:02.51. In her second event, the 200-meter freestyle, she won a silver medal finishing behind world record holder Federica Pellegrini by 1.98 seconds. Schmitt's time of 1:54.96 was good enough for the American record. In the 4×200-meter freestyle relay, she swam the final leg in 1:54.21 as the American team placed second to China. The final time of 7:42.56 was just behind China's time of 7:42.08, but was good enough for the American record.
At the 2011 World Aquatics Championships in Shanghai, Schmitt won a gold medal in the 4×200-meter freestyle relay with Missy Franklin, Dagny Knutson, and Katie Hoff, with the team finishing ahead of Australia and China. As the anchor leg, Schmitt had a 1:56.49 split. Schmitt also competed in the individual 200-meter freestyle and finished sixth in the final (1:56.98).
At the 2012 United States Olympic Trials in Omaha, Nebraska, the U.S. qualifying meet for the 2012 Olympics, Schmitt made the U.S. Olympic team by finishing first in the 200-meter and 400-meter freestyle, and third in the 100-meter freestyle. In the 200-meter freestyle final, Schmitt broke her own American record of 1:54.96 with a time of 1:54.40.
At the 2012 Summer Olympics in London, Schmitt won a total of five medals: three gold, one silver, and one bronze. In her first event, the 4×100-meter freestyle relay, Schmitt won bronze with Missy Franklin, Jessica Hardy and Lia Neal, with the U.S. team finishing third behind the women's relay teams from Australia and the Netherlands. Swimming the anchor leg, Schmitt had a split of 53.54 seconds and the team finished with a total time of 3:34.24, an American record. Schmitt won the first individual Olympic medal of her career, a silver, in the 400-meter freestyle, and in doing so, set the American record for the event. Her time of 4:01.77 was just 0.32 seconds behind winner Camille Muffat. In her second and last individual event, the 200-meter freestyle, Schmitt won gold while setting a new Olympic record of 1:53.61, which was also a new American record. In the race, Schmitt won by a margin of 1.97 seconds over Muffat. In the 4×200-meter freestyle relay, Schmitt earned her second gold after passing Australian Alicia Coutts and topping the field with a split of 1:54.09 as the anchor leg. Also on the winning 4×200-meter relay team were Missy Franklin, Dana Vollmer and Shannon Vreeland. In her final event, the 4×100-meter medley relay, Schmitt won gold with Missy Franklin, Rebecca Soni, and Dana Vollmer. Swimming the freestyle leg, Schmitt recorded a time of 53.25, and the American team went on to set the world record with a time of 3:52.05, bettering the Chinese-owned record of 3:52.19 set in 2009.