After trailing by as much as 13 in the first half, they cut the deficit to one possession on five different occasions, including twice at only two points down.
But the final time OU pulled to within one score at 49-46, Baylor used a 20-13 spurt to go up by double digits with 2:57 remaining.
OU never got back down by single digits again.
Guard Steven Pledger led the way for the Sooners with 17 points on 6-for-12 shooting, including five hits from behind the arc in 10 attempts.
Baylor forward Perry Jones III led all scorers with 25 points on 10-for-13 from the field.
Guard LaceDarius Dunn and forward Quincy Acy were the two other players in doubles for the Bears, with 16 and 15, respectively.
Sooner guard Cade Davis did not play, as his grandmother passed away Tuesday morning.
The loss is OU's 11th straight in conference play dating back to last year, and one more will make it the longest conference losing streak for OU since dropping 15 consecutive contests in the Big 6 back in the 1930-31 season.
OU will attempt to avoid doing so when it faces Texas at 3 p.m. Saturday at the Frank Erwin Center in Austin, Texas.