With the rise of the first team the club's reserve side, TSG 1899 Hoffenheim II, started to climb through the ranks, too. It entered the Verbandsliga Baden in 2001, only a year after the senior team had won this league, and won promotion to the Oberliga Baden-Württemberg in its second season there after coming second in the Verbandsliga.
After seven seasons in the Oberliga where it gradually improved season by season the team won promotion to the Regionalliga Süd after a league title in 2010. With the disbanding of the Regionalliga Süd in 2012 Hoffenheim II became part of the new Regionalliga Südwest.
With the introduction of the Regionalligas in 1994 and the 3. Liga in 2008 as the new third tier, below the 2. Bundesliga, all leagues below dropped one tier. In 2012, the number of Regionalligas was increased from three to five with all Regionalliga Süd clubs except the Bavarian ones entering the new Regionalliga Südwest.