The Netherlands striker scored with 12 minutes remaining to seal a narrow win that leaves S04 in fourth spot and six points adrift of Saturday's hosts
The visitors broke the deadlock through Leon Goretzka's first half strike, but Leverkusen equalised thanks to Felipe Santana's own goal just past the hour mark.
However, a late goal from Huntelaar saw Jens Keller's side take all three points and hand them a boost in the race for Champions League football.
There was controversy surrounding Leverkusen coach Sami Hyppia's decision to drop Schalke-bound Sidney Sam from the starting XI ahead of the clash between the two Champions League chasing clubs.
But the first chance of the game fell to the home side as Stefan Kiessling received the ball from Lars Bender before losing his man and firing a shot straight at Ralf Fahrmann.
Leverkusen continued to push forward and Heung-Min Son latched on to a dinked ball over the top and produced great chest control to create a shooting opportunity, but Fahrmann closed down the angle well.
Schalke had threatened little up until then but looked dangerous on the break, as Jefferson Farfan raced down the right wing and provided a looping delivery for Huntelaar, but he was unable to get purchase on the header.
Sebastian Boenisch came close to opening the scoring as he got on the end of a teasing delivery from Roberto Hilbert, which Joel Matip failed to cut out as Leverkusen pressed for the lead.
However, it was Schalke who broke the deadlock on 28 minutes after a mistake by Lars Bender. The midfielder was caught in possession midway in his own half and Goretzka took full advantage as he surged through on goal, evaded the challenge of Philipp Wollschied and dinked the ball over Bernd Leno.
Leverkusen almost restored parity after the break as Son found space in the box, only for his deflected drive to fly wide of the post.
And it almost got worse for the home side when Farfan's electric pace forced Boenisch into a last-ditch challenge and from the resulting free kick the Peruvian curled the effort narrowly over the crossbar.
But Santana put through his own net and gave the visitors the vital goal they needed. The ball was whipped into the box, causing uncertainty, and the Brazilian took full advantage by rifling past Fahrmann.
However, there was to be a late twist with 12 minutes remaining as Huntelaar made it 2-1 to Schalke and gave Keller's men all three points.