Hoffenheim have won their first three games and hold a three-point advantage over Kaiserslautern, Mainz, Hamburg SV and Hanover 96 at the top of the table.
"We played a good match but unfortunately conceded two goals from set pieces," said Schalke coach Felix Magath.
Defender Isaac Vorsah headed the home team into the lead in the 37th minute after former Real Madrid players Huntelaar and Raul had missed early chances for Schalke.
Huntelaar, who scored five goals in two games for his country over the previous seven days, almost equalised in the second half but goalkeeper Tom Starke spectacularly tipped his effort on to the bar.
OWN GOAL
Hoffenheim sealed the points in injury time when Sejad Salihovic's free-kick hit the post before bouncing in for an own goal off the chest of keeper Manuel Neuer.
Big spenders Schalke went into the game hoping for a boost ahead of Tuesday's Champions League opener against Olympique Lyon.
It only took Raul and Huntelaar, who joined from AC Milan last week, two minutes to combine in the box before the Spaniard's shot sailed just wide.
Eight minutes later it was the unmarked Huntelaar's turn to miss, firing wide from nine metres.
Hoffenheim then spurned two openings of their own through Bosnian striker Vedad Ibisevic before the unmarked Vorsah punished last season's runners-up for some poor defending by nodding in an Andreas Beck cross.
Raul sent a close-range header wide with six minutes left before Neuer's own goal completed Schalke's misery.
