The Italian is the first singles alternate for the 2021 Nitto ATP Finals, having finished in ninth position in the FedEx ATP Race To Turin.

Sinner broke into the Top 10 of the FedEx ATP Rankings for the first time in November 2021. The 20-year-old captured four titles during the season, winning at the Great Ocean Road Open in Melbourne (d. Travaglia), the Citi Open in Washington, D.C. (d. McDonald), Sofia Open (d. Monfils) and European Open in Antwerp (d. Schwartzman).