The Premier Intermediate League returned after a one-year hiatus, following the cancellation of the 2020–21 season due to the COVID-19 pandemic in Northern Ireland. Annagh United were the reigning champions from the 2019–20 season, and were promoted to the NIFL Championship. The season began on 17 August 2021 and concluded on 7 May 2022.
Source: Premier Intermediate Legend: Blue = home team win; Yellow = draw; Red = away team win. For upcoming matches, an "a" indicates there is an article about the rivalry between the two participants.