The season began on 3 September 2021 and ended on 10 April 2022.
[1] Nadur Youngsters won the league title.
The bottom-placed team (SK Victoria Wanderers) were relegated to the 2022–23 Gozo Second Division.
Nadur Youngsters entered the season as defending champions.
The seventh-placed team (Sannat Lions) faced the second-placed team from the 2021–22 Gozo Second Division (Munxar Falcons) for the final place in the 2022–23 Gozo First Division.