Kelty Hearts were the reigning champions but were unable to defend their title after gaining promotion to Scottish League Two.
Bonnyrigg Rose Athletic won their first league title on 1 March 2022 thanks to a 5–0 win over Cumbernauld Colts at New Dundas Park, with five matches still to play.
They faced the winners of the 2021–22 Highland Football League (Fraserburgh) in the Pyramid play-off, winning 3–2 on aggregate.
[2] The proposal was given provisional approval by the majority of member clubs, with the vote being confirmed at the league's AGM on 27 May 2021.
A three-match round robin play-off took place between the winners of the 2021–22 East of Scotland Football League (Tranent Juniors), the 2021–22 South of Scotland Football League (St Cuthbert Wanderers), and the 2021–22 West of Scotland Football League (Darvel).