The win broke a 16-game conference road losing streak for the Cowboys (13-12, 4-7 Big 12) and snapped a five-game winning streak for the Aggies (20-5, 6-4 Big 12).
The Aggies started the game strong, moving out to a 18-9 lead at the ten minute mark of the first half.
The Cowboys came back to tie the game 28-28 with four minutes left in the half.
It stayed close for the rest of the first half, with the Aggies taking a slim 36-34 halftime lead.
At the half, Joseph Jones and DeAndre Jordan had each made 5 of 6 from the field and scoring 11 points to lead the Aggies at the break. Guards Byron Eaton and Obi Muonelo had each scored 8 points for the Cowboys.
The Aggies scored just three points in the first seven minutes of the second have as Oklahoma St to a 43-39 lead.
Texas A&M regained the lead, 46-45, on a 3-point jumper by Derrick Roland with ten minutes left in the game. That was to be the Aggies last lead of the day.
The Aggies cold second half continued, scoring just eight points in the last ten minutes of the game, as Oklahoma St pulled away for a 59-54 upset of Texas A&M.
For one of the first times this season, Texas A&M was out-rebounded, 27-21 by the Cowboys.
Oklahoma State was led by their guard tandem of Byron Eaton and Obi Muonelo. Eaton scored 17 points while Muonelo 15 points and pulled down 7 rebounds.
Freshman DeAndre Jordan was one of the few bright spots for the Aggies, coming off the bench to score 15 points.
The game was played in front of a record crowd of 13,584, including former Texas A&M All-America Acie Law IV. Law, who plays for the Atlanta Hawks, was honored in a halftime ceremony in which a banner of his jersey was raised to the rafters of Reed Arena. It was the first time Texas A&M honored a player that way.
The Aggies must quickly regroup as they travel to Austin to face No 10 Texas on Monday night.