The 1921–22 season was the 24th in the history of the Southern League.
[1] Plymouth Argyle reserves won the English section, whilst Ebbw Vale won the Welsh section.
Plymouth Argyle reserves were declared champions after defeating Ebbw Vale 3-0 in a championship play-off.
[2] Pontypridd and Bath City were the only two Southern League clubs to apply for election to the Football League, though neither was successful.
Newly elected teams: In addition to the two clubs finishing bottom of Football League Third Division South, three non-League clubs joined the election process, of which two were from the Southern League.