The Wildcats hit 10-of-24 3-pointers in knocking off the Sooners 69-60 and sending them home with their first conference loss of the season.
They dropped to 3-1 in Big 12 play, with K-State rising to 4-0.
Osby, with his furious slam, led the Sooner scoring attack with 12 points on 5-of-9 shooting, while forward Amath M'Baye produced 12 points on identical shooting.
Guard Steven Pledger, the catalyst in two Sooner victories over the Wildcats last year, also finished in double figures with 10.
K-State guard Rodney McGruder led all scorers with 20 points, including a game-high four hits from behind the arc.
OU actually out-boarded K-State 39-25 and outshot the home Wildcats 47.2 percent to 44 percent.
But 16 turnovers and 26 points off those allowed the Wildcats to triumph in a game that featured 11 lead changes.
The Sooners get back to action when they host Red River Rival Texas (8-9, 0-4 Big 12) at 8:30 p.m. Monday at Lloyd Noble Center.