Hosts Schalke, who had enjoyed a fine start before imploding in the last two months, snatched the winner with in-form striker Eric-Maxim Choupo-Moting flicking in a pin-point Johannes Geis cross in the 28th minute.
Hoffenheim, with former Schalke coach Huub Stevens on the bench, twice came close to an equaliser but both times Chile international Eduardo Vargas fired over the bar to leave the visitors second-bottom on 13 points.
Schalke, who have 27 and sit two behind third-placed Hertha Berlin, also had other chances with Sead Kolasinac rattling the post with a powerful shot early in the second half.
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Leaders Bayern Munich, five points clear at the top, travel to Hanover 96 on Saturday with second-placed Borussia Dortmund, on 38 points, visiting Cologne.
(Reporting by Karolos Grohmann, editing by Mark Meadows)
