[5] Struff got to the semifinals in the Australian Open men's doubles in partnership with Ben McLachlan, including a win over the No.

[6] At the 2018 Wimbledon Championships, he reached the quarterfinals in doubles, also partnering with McLachlan, where they lost to the wildcard pair of Frederik Nielsen and Joe Salisbury.

In Tokyo, Struff defeated Marin Čilić and had a match point in the second set of his quarterfinal encounter against Denis Shapovalov.

[10] However, in doubles, he and his partner, Ben McLachlan, won the title, beating Raven Klaasen and Michael Venus in the final.

[52] However, in doubles, he and his partner, Henri Kontinen, reached the final where they lost to Pierre-Hugues Herbert and Nicolas Mahut.

[55] Representing Germany in the Davis Cup tie against Belarus, he won both of his rubbers by beating Ilya Ivashka and Egor Gerasimov.

[57][58] When the ATP Tour resumed tournament play in August, Struff competed at the Western & Southern Open.

This event usually takes place in Cincinnati but this year, it was held at the USTA Billie Jean King National Tennis Center in New York City in order to reduce unnecessary player travel by centralizing the tournament and the subsequent US Open in the same venue.

[72] In February, he represented Germany with Alexander Zverev, Kevin Krawietz and Andreas Mies at the ATP Cup.

[76] Seeded eighth at the Open Sud de France, Struff was defeated in the first round by qualifier and compatriot, Peter Gojowczyk.

[118] Germany ended in third place in Group C. At the Adelaide International 2, he lost in the first round to qualifier Corentin Moutet.

[121] Representing Germany in the Davis Cup tie against Brazil, he played one match and lost to Thiago Monteiro.

[124] Seeded fourth at the Arizona Tennis Classic, an ATP Challenger event, he was eliminated in the first round by lucky loser and compatriot, Mats Moraing.

However, in doubles, he and his partner Oscar Otte reached the final and lost to Treat Huey and Denis Kudla.

[125] At the Miami Open, Struff retired during his first-round match against Pedro Martínez due to a right foot injury.

He also won the doubles title with Marcelo Demoliner by defeating Roman Jebavý and Adam Pavlásek in the final.

[140][141] Getting past qualifying at the Sofia Open, he reached the quarterfinals where he was defeated by fourth seed Lorenzo Musetti.

Struff played his final event of the year by representing Germany in the Davis Cup quarterfinal tie against Canada.

[149] At the Madrid Open, he qualified for his fourth consecutive Masters as a lucky loser, where he reached also the second round defeating Lorenzo Sonego.

[150][151] He reached the semifinals of a Masters for the first time in his career upsetting fourth seed Stefanos Tsitsipas for his second top-5 win of the season.

He became the third lucky loser to advance to the semifinals of a Masters event, joining Thomas Johansson (2004 Toronto) and Lucas Pouille (2016 Rome).

Struff then played in Halle, where he beat Roman Safiullin before losing to eventual champion Alexander Bublik.

After a three months break he returned to the Asian swing at the Zhuhai Championships where he lost to eventual finalist Yoshihito Nishioka in the quarterfinals.

He won his first round match, snapping a four-match losing streak, at the Swiss Indoors in Basel defeating Christopher Eubanks.

As the 24th seed, he won his first match in 6 years at the Australian Open, beating Rinky Hijikata in 5 sets, but lost to Miomir Kecmanović in the second round.

In Rotterdam, Struff reached the round of 16, defeating Alejandro Davidovich Fokina,[158] before losing to Emil Ruusuvuori.

At his next tournaments, Struff had less success in singles, losing in the first round of Doha to Christopher O'Connell and in Dubai Tennis Championships to Hubert Hurkacz.

[159] He made a back-to-back appearance in the third round of Indian Wells, where he beat Borna Ćorić but lost to Jannik Sinner.

In the beginning of the clay court season in Monte-Carlo, he reached the third round by defeating Sebastián Báez and Borna Ćorić before again losing to Jannik Sinner.

[4] He also reached the final of the doubles event, partnering Andreas Mies, where he lost to Yuki Bhambri and Albano Olivetti.