Before turning 16, Harrison was regarded as a prodigy after cracking the top 10 in the junior rankings and becoming one of the youngest players ever to win an ATP match.

Harrison built on that momentum in 2017 to reach a top-40 career-high ranking in singles after winning his first career ATP title.

[1] Harrison has a younger brother Christian, who currently plays tennis on the ATP Challenger Tour.

Harrison is notable for being the third-youngest player since 1990, after Richard Gasquet and Rafael Nadal, to have won an ATP level match, defeating world no.

[4] This puts Harrison among an elite group and makes him the youngest American to accomplish this feat since Michael Chang.

In June, Harrison would win his first futures title, defeating another rising star Filip Krajinović in the final.

Directly after that final, Harrison made it to the semifinals of a Challenger tournament in Sacramento, losing to Jesse Levine.

Afterwards, Harrison went through qualifying in the 2010 Delray Beach International Tennis Championships, then lost to eventual champion Ernests Gulbis in the first round.

Harrison received a wildcard for the 2010 BNP Paribas Open, where he defeated Taylor Dent in the first round, before losing to the eventual winner Ivan Ljubičić.

263 in the world, Harrison entered the qualifying tournament for the 2010 French Open, after having lost in the final of the US Wildcard Playoff to Ryan Sweeting.

Having not gained any points on his favorite surface, Harrison decided to compete in the 2010 Hall of Fame Tennis Championships.

Harrison qualified for the US Open and defeated the 15th seed Ivan Ljubičić in the first round for his first win in a Grand Slam tournament.

In the second round, Harrison fell to Sergey Stakhovsky in a grueling 5-setter, after failing to convert three match points when up 6–3 in the fifth set tiebreak.

He ousted 22nd-seeded Guillermo García López in the second round of the 2011 BNP Paribas Open at Indian Wells, California, as a wild card.

In the third round, he defeated Canadian up-and-comer Milos Raonic in a tight three-setter to set up a fourth-round confrontation with world no.

He then competed in the qualifying competition for Wimbledon, in which he reached the final round but lost in five sets to Cedrik-Marcel Stebe.

He faced seventh seed David Ferrer in the second round, losing in a five-set match that lasted two days.

With partner Matthew Ebden, he won the doubles tournament at the 2011 Campbell's Hall of Fame Tennis Championships in July.

In February, Harrison made his third appearance in the semifinals in San Jose, where he lost to eventual winner Milos Raonic.

In April, Harrison lost his inaugural Davis Cup matches to France's Jo Wilfried Tsonga and Gilles Simon.

Harrison played for the Philadelphia Freedoms of World Team Tennis in the summer as their 2012 wild-card player.

After qualifying in Brisbane and Sydney, he exited in the first round of both tournaments at the hands of Sam Groth and Nicolas Mahut, respectively.

In Memphis and Delray Beach, he made it to the second round with victories over Björn Phau and Yen-Hsun Lu, but then lost to Alex Bogomolov Jr. and Marin Čilić.

At the US Open, he achieved the biggest win of his career by knocking off 5th-seeded Milos Raonic to reach the 3rd round of a grand slam for the first time ever.

Playing for the San Diego Aviators, Harrison was named 2016 World TeamTennis Male Most Valuable Player.

[10] Harrison won his first match at the Australian Open over Frenchman Nicolas Mahut 6–3, 6–4, 6–2, marking the first time he made the second round at the tournament since 2013.

Harrison reached the final of the RBC Tennis Championships of Dallas and defeated Taylor Fritz in straight sets, winning his fourth Challenger title.

Between his back-to-back titles at the RBC Tennis Championships of Dallas and the Memphis Open, he did not drop a set at either tournament.

During competition in the 2018 New York Open, Harrison was charged by competitor Donald Young with making racist comments during their match.

[14][15] He made his return to the tour at the 2020 Delray Beach Open as a wildcard, after being out due to surgery, and won his first match since April 2019 in Houston, defeating Damir Džumhur.