At 6 feet 11 inches (2.11 m), he is tied (with Ivo Karlović) for the tallest-ever ATP-ranked player, and can produce serves that measure over 140 miles per hour (225 km/h).

[4] He credits Tom Gullikson, whom his father knew from playing golf, for much of his early development as a tennis player.

[8] Opelka made his ATP debut at the 2016 U.S. Men's Clay Court Championships, where he lost in the first round to fifth seed Sam Querrey.

He continued his momentum with first round wins at the Los Cabos Open and the Cincinnati Masters where he defeated Sergiy Stakhovsky and Jérémy Chardy respectively to move into the top 300 of the ATP rankings.

After struggling with a foot injury towards the end of the summer, Opelka returned to the USTA Pro Circuit for the indoor season and won his first ATP Challenger title in Charlottesville to finish the year just outside the top 200.

At the Memphis Open, he recorded his only ATP Tour level win of the year over fellow Next Gen American Jared Donaldson.

His solid performance on the ATP Challenger Tour earned him his first top-100 year-end finish in singles, ending the season at world No.

[13] In February, Opelka again defeated Isner, saving six match points, en route to his first ATP title at the New York Open.

At Wimbledon in July, he achieved his best Grand Slam result to date, reaching the tournament's third round and defeating Stan Wawrinka in the process.

In February, Opelka lifted his second career trophy at the Delray Beach Open after saving a match point in the semifinals against Milos Raonic.

He instead began the season at the Great Ocean Road Open as the sixth seed, but lost to Botic van de Zandschulp in the second round.

At the Australian Open, he beat Lu Yen-hsun before losing to 27th seed Taylor Fritz, despite holding match points in the fourth set.

In Rome, Opelka beat Richard Gasquet, Lorenzo Musetti, Aslan Karatsev and Federico Delbonis to reach his first Masters semifinal, where he lost to Rafael Nadal.

[15] Seeded 32nd at the French Open, Opelka beat clay-court specialists Andrej Martin and Jaume Munar to reach the third round, his best showing at this Grand Slam event, where he lost to Daniil Medvedev.

[16] Partnering Jannik Sinner, he won his first doubles title at the Atlanta Open defeating Steve Johnson and Jordan Thompson.

[30] At the 2022 U.S. Men's Clay Court Championships, Opelka won his second title of the year and fourth of his career, defeating compatriot John Isner in what was the tallest ATP Tour final in the Open Era.

[34] In the quarterfinals he defeated Mackenzie McDonald in three sets to become the lowest ranked player in history to make an ATP level semifinal[35][36] where his run came to an end against Alex Michelsen.

[43] Despite these injury concerns, he made a victorious start at the Australian Open, defeating Belgian Gauthier Onclin in the first round.