[5] Coached by Sam Winterbotham and Chris Woodruff, the younger Sandgren immediately strengthened the middle of the Vols' singles lineup, going 10–0 in Southeastern Conference play at the No.

As a sophomore, Sandgren reached the semifinals of the NCAA Singles Championships, losing to teammate, roommate and doubles partner Rhyne Williams in three sets.

In 2013, his ATP ranking remained inside the top 300 for nearly the entire year, allowing him to play on the Challenger Tour for much of the season.

Sandgren returned to the Top 200 in November 2016, when he reached his second career Challenger final in Columbus, almost three years after he first achieved these two milestones.

He qualified for his first tournament on the ATP World Tour, the U.S. Men's Clay Court Championships in Houston.

He recorded his first two ATP World Tour wins at the Washington Open in early August, including a victory over No.

Sandgren received entry into the main draw of the tournament as a lucky loser following the withdrawal of Kyle Edmund.

In the first round of the main draw, he lost in three sets to Hyeon Chung, winner of the inaugural Next Generation ATP Finals in Milan, Italy, two months prior.

In the second round, he defeated 2014 champion and ninth seed Stan Wawrinka, marking his first victory against a Top 10 ranked player.

[13] In the run up to the quarterfinal he was involved in controversy when he was publicly criticized by Serena Williams for making anti-LGBTQ comments.

Sandgren lost in the first round of the Monte Carlo Open to Philipp Kohlschreiber in straight sets.

In the first round of Wimbledon, Sandgren was knocked out by eventual champion Novak Djokovic in straight sets, winning only six games.

Sandgren again made it to the quarterfinals of the 2020 Australian Open, where he lost in five tight sets against Roger Federer, after having seven match points.

[16] Having tested positive for COVID-19 in November 2020, Sandgren returned the same result in January 2021, but was deemed to be "non-infectious" and was allowed entry into Australia to compete in the Australian Open where he lost in the first round.

[20] When Novak Djokovic had his Australian visa rescinded upon arrival to play in the tournament, Sandgren's comment on Twitter in response to the Victorian state government's position on the matter was "LOL trusting the science again".

Sandgren has played two seasons with World TeamTennis starting in 2015 when he debuted in the league with the California Dream and then again in 2018 with the Washington Kastles.