Eric Maxim Choupo-Moting looked to gave his side the perfect start with an early opener, but that was as good as it got for the Royal Blues.
Entertaining opening period sees Hoffenheim take lead into break
Schalke got off to just the start they needed in order to relieve pressure on Weinzierl, and it was through the man he opted to play out on the right. Embolo burst down the flank with superb pace before whipping in an equally good cross to the back post. Choupo-Moting was diving in ahead of Süle to bullet a header past the helpless Oliver Baumann.
Hoffenheim hit back and almost equalised in style as Rupp threaded a brilliant pass into the path of Kramaric. The striker couldn't get his chip to come down in time, though.
That would turn out to be just a minor blip and the Croatian forward made amends almost immediately. Pavel Kaderabeck was afforded for too much time to get down the left and put in a perfect ball to Kramaric. He managed to evade the attentions of Abdul Baba Rahman and Matja Nastasic to power home into the bottom corner.
Schalke came back into the game and didn't let their heads drop, and it was from a header where they almost went ahead again. A corner was taken short to Baba Rahman, and the Ghana left-back picked out a Klaas-Jan Huntelaar with a fine delivery. His headed effort came back of the bottom of the post, much to his annoyance.
Hoffenheim were dealt a further blow when Ermin Bicakcic went off injured, with Fabian Schär his replacement. That didn't affect the Sinsheim side too much as they took the lead for the first time through Rupp. Kerem Demirbay went on a great run after Nabil Bentaleb gave the ball away, and a simple pass to the back post was tapped in by Rupp.
Scoreless second half suits Hoffenheim as they claim three points
The second half began with both sides playing slightly more reserved than that in the first period. Chances were hard to come by as a result, especially for Schalke, but Hoffenheim eventually got things going in an attacking sense. Mark Uth and Kramaric's long-range efforts were off target, however.
In truth, it was Hoffenheim who were in full control. They may not have enjoyed the possession to show it, but Schalke's attack looked limp and lifeless with Max Meyer and Alessandro Schöpf being brought on to little effect. That meant the hosts were free to break and counter at will, yet they couldn't make it count.
Schalke had a late, perhaps very convincing, penalty appeal turned down but it was to prove Hoffenheim's day as they saw out the remaining minutes with relative ease. They're now seventh with that win and look set for a much better season than last, while Schalke are off to their worst start in their Bundesliga history and sit bottom without a point.