Shortly after the formation of the league, the Nazis reorganised the administrative regions in Germany, and the Gaue Hesse Nassau and Saar-Palatinate (later: Westmark) replaced the old states and provinces.

The Gauliga Südwest/Mainhessen was established with twelve clubs from the states of Prussia, Bavaria, Hesse and Saarland.

The imminent collapse of Nazi Germany in 1945 gravely affected all Gauligas and football in Hesse at this stage had a very low priority.

The league operated with nine clubs since FK Pirmasens withdrew early and two relegated team.

The last season in 1944-45 was probably not started at all as much of Lorraine had been reoccupied by allied forces and the rest of the Reichsgau Westmnark was a front line zone.

In the US zone, football soon resumed and the Oberliga Süd was formed in late 1945 as a replacement for the Gauligas in the south of Germany.

The clubs from the Südwest/Mainhessen region did not win a national championship in the Nazi era but achieved two finals appearances.