Since the age of 9, Keys has been part of the Chris Evert Academy in Boca Raton, Florida. She is one of the youngest tennis players to win a match on the WTA Tour, at the age of 14 years and 48 days, by beating world No. 81 Alla Kudryavtseva on the clay courts at the 2009 MPS Group Championships in her home state of Florida.
During her early years, Keys played mostly on the ITF tour, where she won three titles in singles and one in doubles.
Keys's first appearance on the WTA Tour came at the 2009 Ponte Vedra Beach Championships, where she received a wildcard into the main draw. She beat world no. 81 Alla Kudryavtseva in the first round, but she was then defeated by top seed Nadia Petrova in straight sets. In July 2009, Keys played World Team Tennis as a member of the Philadelphia Freedoms. Still only 14 years old, she beat reigning Wimbledon champion Serena Williams in women's singles by a score of 5–1.
In 2011, Keys won a spot in her first US Open by beating Beatrice Capra in the finals of an eight-player wildcard playoff. Keys won her first match, beating fellow American Jill Craybas, but then lost in three sets to world #27 Lucie Šafářová.
In 2012, Keys won another wildcard competition amongst American players, this time for the 2012 Australian Open. However, she then lost in the first round to 2010 semi-finalist, Zheng Jie.
After losing in qualifying at her first event in Auckland, Keys reached the quarterfinals at a WTA event for the first time in 2013 Apia International Sydney, defeating Lucie Šafářová and Zheng Jie, avenging earlier Grand Slam losses to both players. She then lost to world #6 Li Na in three close sets. At the 2013 Australian Open, Keys beat Casey Dellacqua and 30th seed Tamira Paszek, before bowing out to 5th seed Angelique Kerber
After reaching the second round in both Indian Wells and Miami, Keys reached the quarterfinals in Charleston before losing to Venus Williams. Keys then claimed her first top ten win in 2013 Mutua Madrid Open Madrid, avenging her Sydney loss to Li Na, before losing to Anabel Medina Garrigues in the second round. Keys completed her clay court season at the 2013 French Open, winning her debut match at the event over Misaki Doi before losing to Monica Puig in straight sets.
Moving on the grass court season, Keys reached the quarterfinals at the Aegon Classic, beating Lesia Tsurenko, Jamie Hampton and Mona Barthel, before falling to Magdaléna Rybáriková. She later reached the third round at Wimbledon, before falling to world #4 Agnieszka Radwańska in three sets.
During the US hardcourt season, Keys won main draw matches at Stanford and Washington DC, but was defeated in the first round at the US Open by Jelena Janković. Keys finished her year at the HP Open in Osaka, and reached her first WTA semifinal, before losing to eventual champion Samantha Stosur. After a successful year on the tour, Keys finished 2013 ranked 37, an improvement of 112 places from 2012.
Keys started the season reaching her first Premier semifinal in Sydney, cruising past Simona Halep in the process, but eventually losing to Angelique Kerber. At the Australian Open, Keys lost to Zheng Jie in the second round, after dropping a double break advantage in the final set. Until May, Keys had only once won back-to-back matches. It was in Miami, when she reached the third round, losing to Li Na, despite serving and having three set points to take a one set lead. In the Internationaux de Strasbourg she reached the semifinal, where she lost to Monica Puig in straight sets. At the French Open she lost in the first round to tenth seed and clay court specialist Sara Errani in three tight sets.
Keys won her first singles title at the Premier event in Eastbourne, beating two top ten players, first Jelena Janković and then Angelique Kerber in a three set final. At the Wimbledon Championships Keys followed that form to reach the third round, taking revenge on Puig for her earlier loss, and then beating 31st seed Klára Koukalová. Her run came to an end in the third round, when she was forced to retire against Yaroslava Shvedova before a second set tiebreak due to a leg injury.
She took a two-week hiatus from tennis to focus on rehabbing her leg. Keys lost her opener in her first tournament back, in the Washington, D.C., before playing two matches at the Rogers Cup in Montreal. In Cincinnati she beat an in-form Alizé Cornet, before pushing Maria Sharapova to three sets in the second round. At the US Open Keys was seeded for the first time at a Grand Slam, at number 27, but had a disappointing second round loss to Serbian qualifier Aleksandra Krunić, a match where both players had won the same amount of points.
Keys played four events in Asia, but didn't mark good results. Namely, she won only two matches at the first three events in Tokyo, Beijing and Wuhan. In the last tournament of the season in Osaka, she reached the quarterfinals and there she retired in the second set against Luksika Kumkhum.
Keys finished the season ranked 31 in the world, improving on 2013 by six places. In November, Keys secured the services of two coaches, former American world number one Lindsay Davenport and husband Jon Leach.
At the Australian Open, Keys reached her first Grand Slam semifinal, defeating three seeded opponents along the way. First, she defeated 29th seed Casey Dellacqua in three sets in the second round, then followed it up by upsetting reigning Wimbledon champion Petra Kvitová in straight sets in the third round. After beating fellow American Madison Brengle in the fourth round, she defeated 18th Venus Williams in the quarterfinals in three sets, despite appearing to be injured during the second set. She then faced world number one Serena Williams in the semifinals, and although she played very well, she lost the match in straight sets, after saving the first eight match points. After the match, Williams, who eventually went on to capture the title, spoke of a bright future for Keys, saying: "It was an honor for me to play someone who will be No. 1 in the future."
After some struggles in Indian Wells and Miami, where she won just one match, she found her form again in Charleston, reaching final without dropping set. However, there she lost to Angelique Kerber, despite having 4–1 lead in the third set. Seeded for the first time at a Grand Slam at the French Open as the 16th seed, Keys made it to the third round before falling to 23rd seed Timea Bacsinszky in straight sets. At Wimbledon Keys was seeded 21st. She defeated Stefanie Vögele, Elizaveta Kulichkova, Tatjana Maria and qualifier Olga Govortsova to advance to the quarterfinals, where she lost to 2012 Wimbledon runner-up Agnieszka Radwanska.
At the 2015 US Open, Keys advanced to the fourth round, where she was defeated by Serena Williams in straight sets. In December, Keys split from her coaches Lindsay Davenport and husband Jon Leach.
At the Australian Open, an injury-affected Keys reached the fourth round before losing to Chinese qualifier Zhang Shuai. After a brief stint with Jesse Levine and Mats Wilander earlier in the year, Keys subsequently hired Thomas Högstedt to be her coach in April.
In May, a week before the French Open, Keys defeated two Top 10 players in Petra Kvitová and Garbiñe Muguruza to reach the biggest final of her career at Rome, where she lost to compatriot Serena Williams in straight sets. At the French Open, Keys was seeded fifteenth. She defeated Donna Vekić, Mariana Duque Mariño and Monica Puig all in straight sets before falling to unseeded Dutch player Kiki Bertens in the fourth round.
She followed up a strong clay court season with an excellent grass court season, highlighted by her second career title at the Aegon Classic in Birmingham. With that victory, she moved into the Top 10 for the first time in her career. Seeded ninth at Wimbledon, Keys easily defeated Laura Siegemund in the first round in straight sets, then prevailed in her next two matches over Belgian Kirsten Flipkens and Frenchwoman Alizé Cornet to advance to the fourth round, where she was defeated by fifth seed Simona Halep.
In July, Keys reached her second Premier 5 final of the year at the Rogers Cup at Montreal, losing in straight sets to Simona Halep. At the US Open as the eighth seed, Keys began her campaign by coming back from a set down to defeat compatriot Alison Riske, followed by a straight sets victory over Kayla Day. In the third round, Keys managed to hold off and defeat Japanese teenager Naomi Osaka, despite being down 1-5 in the third set and Osaka serving for the match twice. She was defeated in the fourth round by former world No. 1 Caroline Wozniacki, meaning Keys reached the fourth round of all four Grand Slam tournaments in 2016, but lost all four of her fourth-round matches. She clinched a spot in the WTA Finals by reaching the semifinals in back-to-back weeks at Beijing and Linz. Making her debut at the event, Keys won one of three matches and did not advance out of the round-robin stage.
During the off-season, Keys rekindled her relationship with former coach Lindsay Davenport and called her back onto her coaching team.
Madison Keys missed the Australian Open due to a left wrist surgery. Keys returned to the tennis scene in March, at the 2017 BNP Paribas Open in Indian Wells. She beat Mariana Duque Marino in straight sets in her first match since the 2016 WTA Finals and followed it up with another straight-sets win over Naomi Osaka, before succumbing to 13th seeded Caroline Wozniacki. Keys then played the 2017 Miami Open where she beat Viktorija Golubic in straight sets before losing to number 72 in the world Lara Arruabarrena despite having set points in the first set and being up a break in the second. Keys called for the trainer for a shoulder injury at 6-5 in the first set.
Keys began the clay court season in Charleston for the 2017 Volvo Car Open where she was the top seed. She lost in the first round to fellow American Shelby Rogers in three sets, despite winning the first. Her next tournament was the 2017 Mutua Madrid Open, where she again lost in the first round to Misaki Doi. At the 2017 Internazionali BNL d'Italia Keys was the defending finalist after losing to Serena Williams in the final last year. She lost in the first round again to Daria Gavrilova.
Despite entering the 2017 Bank of the West Classic with only six wins on the season due to struggles with injuries, Keys won the tournament after knocking out Wimbledon champion Garbiñe Muguruza in the semifinals and close friend CoCo Vandeweghe in the final.
Keys reached her first Grand Slam final at the 2017 US Open, beating Elise Mertens, Tatjana Maria, 17th seed Elena Vesnina, 4th seed Elina Svitolina, qualifier Kaia Kanepi and 20th seed CoCo Vandeweghe. Bidding to become the first American US Open champion not named Williams since 1998 where her coach Lindsay Davenport won it, Keys lost to her close friend Sloane Stephens in straight sets.
Keys's passion for tennis started at a young age while growing up in the Quad Cities. She first became interested in tennis because she liked Venus Williams's white tennis dress, according to a video interview she conducted with World Tennis Magazine in August 2011. Her parents are Rick and Christine (attorneys), and her siblings are Sydney, Montana, and Hunter.