The South Challenge Cup is for member clubs of the East of Scotland Football League, Scottish Lowland Football League, South of Scotland Football League and West of Scotland Football League.

The first and second rounds will be regionalised into four zones, with Thornton Hibs in the 'North-East Zone'.

First Round - Saturday 11th September 2021
Second Round - Saturday 16th October 2021
Third Round - Saturday 20th November 2021
Fourth Round - Saturday 5th February 2022
Fifth Round - Saturday 5th March 2022
Sixth Round - Saturday 2nd April 2022
Semi-Finals - Saturday 30th April 2022
FINAL - Sunday 22nd May 2022