Marcus Denmon scored a team-high 17 points as 65 victory at Mizzou Arena.
Ricardo Ratliffe added 15 points and 12 rebounds, Michael Dixon scored 15 points as well, and Phil Pressey and Kim English each netted 13 for Missouri (24-2, 11-2 Big 12), which won its sixth straight contest.
The Tigers now sit in a tie with Kansas for the top spot in the conference.
Keiton Page scored a game-high 23 points for the Cowboys (12-14, 5-8), who lost for the fourth time in six games.
"You know, Missouri [didn't] play like the third-ranked team in America tonight. They actually played like the No. 1-ranked team in America tonight," Oklahoma State head coach Travis Ford said.
Oklahoma State opened the game with a Markel Brown three-pointer and held the lead over the first five minutes until a 20-2 run by the Tigers put them ahead for good.
Missouri stretched its advantage to as many as 22 points twice in the first 20 minutes, with the second coming from an English layup that gave the Tigers a 44-22 lead at the half.
"We came out early and really got stops midway through the first half, and we executed and played really well out of transition," said English.
Missouri then cruised through the second half, leading by as many as 35 points and by at least a 17 en route to the easy win.
The Tigers hold a 76-41 advantage in the all-time series, including a 45-7 lead in Columbia...Oklahoma State fell to 23-51 all-time against opponents nationally ranked in the top-five...The Tigers held a 37-29 advantage on the glass.