Marcus Smart had 18 points, and Phil Forte added 16 points -- making 4 of 7 from three-point range -- for Oklahoma State (11-1), which shot 52 percent from the field overall and 62 percent in the second half.
Le'Bryan Nash had 15 points, six rebounds, and three blocked shots as the Cowboys' win snapped Colorado's 10-game winning streak. Brown scored 11 points from the free-throw line to lift Oklahoma State to its fourth straight win.
Josh Scott led Colorado (10-2) with 20 points, 12 rebounds, and three steals. Askia Booker scored 19 points and Spencer Dinwiddie added 18.
Oklahoma State built its lead to 63-53 with 7:36 remaining. Colorado chipped away and brought the deficit down to four points twice in the final minute, but couldn't get any closer.
Oklahoma State built two six-point first-half leads, including at halftime. The Buffaloes briefly led 7-4 in the first half as they only went 1 of 2 from the free-throw line.
Booker had 13 first-half points for Colorado, which trailed 32-26 at halftime. The Cowboys took the lead for good with 1:37 left in the opening half.
Colorado will be back at the MGM Grand Arena for the Pac-12 Conference Tournament in March.
The Cowboys now lead the all-time series 61-48.
The teams last met nearly three years ago with the Buffaloes winning 75-71 in January 2011. The last time the teams met on a neutral court was in March 2005 at the Big 12 Conference Tournament in Kansas City.
Colorado hasn't beaten a Top 10 team on a neutral floor since 1990 at the Big Eight Tournament in Kansas City.