2022 U.S. Men's Clay Court Championships – Singles

Reilly Opelka defeated John Isner in the final, 6–3, 7–6(9–7), to win the singles tennis title at the 2022 U.S. Men's Clay Court Championships. It marked Opelka's fourth career Association of Tennis Professionals (ATP) singles title and his first on clay. With Opelka's height at 6ft 11in and Isner's at 6ft 10in, the combined heights of both players made the final the tallest one ever contended during the Open Era. At the age of 36, Isner was also playing to become the oldest champion at the tournament in the Open Era.

Cristian Garín was the defending champion from when the tournament was last held in 2019, but lost in the semifinals to Isner.

Seeds
The top four seeds received a bye into the second round. • #🇳🇴 Casper Ruud (withdrew due to tooth pain)

• #🇺🇸 Taylor Fritz (quarterfinals)

• #🇺🇸 Reilly Opelka (champion)

• #🇺🇸 John Isner (final)

• # Cristian Garín (semifinals)

• #🇺🇸 Frances Tiafoe (quarterfinals)

• #🇺🇸 Tommy Paul (second round)

• #🇺🇸 Jenson Brooksby (first round)

Seeds
• # Tomás Barrios Vera (first round)

• # 🇺🇸 Bjorn Fratangelo (first round)

• # 🇺🇸 Mitchell Krueger (qualified)

• # 🇦🇺 Max Purcell (qualified)

• # 🇺🇸 Michael Mmoh (qualifying competition, lucky loser)

• # Gonzalo Lama (first round)

• # 🇨🇦 Steven Diez (qualifying competition, lucky loser)

• # 🇺🇸 Christian Harrison (qualified)

Qualifiers
• # Gijs Brouwer

• # 🇺🇸 Christian Harrison

• # 🇺🇸 Mitchell Krueger

• # 🇦🇺 Max Purcell

Lucky losers
• # 🇨🇦 Steven Diez

• # 🇺🇸 Michael Mmoh