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The league came into existence under the 'South' name for the 2006–07 season, although a 'Lothian District league' had been in place below the East Super League since 2002–03, using the structure of a common 'East Region' top tier and lower regional divisions in place of the old structure of three separate regional leagues in that part of Scotland, with the East Junior Football League the historic Lothians competition. The South Division was expanded for the start of the 2013–14 season by absorbing the more southerly clubs from the dissolved East Region Central Division as part of league reconstruction in the region.
Between 2006–07 and 2017–18, there was an East Premier League at tier 2 and North and South Divisions at tier 3. The large-scale movement of clubs to the East of Scotland League resulted in the structure being flattened into two tiers. Further league reconstruction for the 2019–20 season split the Super League into North and South divisions, reducing the number of Premier League South teams. For the final season it comprised 10 clubs who were due to play each other three times to give 27 league fixtures prior to the season being cancelled due to the COVID-19 pandemic.
^ Season suspended in March 2020 due to the coronavirus pandemic, later officially declared null and void with no champion declared. Using 'points per game' algorithm applied in other leagues, Stoneyburn would have been nominal champions.
Camelon were promoted to the Super League. Runners-up Penicuik Athletic were promoted to the new Premier League, along with Musselburgh Athletic (3rd) and Armadale Thistle (4th).