Davidovich Fokina missed the 2021 Australian Open after testing positive for COVID-19. At the 2021 Monte-Carlo Masters, he achieved his first win over a top 10 player as he beat Matteo Berrettini 7-5, 6-3. After beating Lucas Pouille 6-2, 7-6 to reach his first ever Masters 1000 quarterfinal, he retired against Stefanos Tsitsipas due to injury.