Senior captain and shortstop Jack Mayfield got the rally started in the top of the eighth with a leadoff single before center fielder Craig Aikin moved him into scoring position with a successful sacrifice bunt.
Then, Texas closer Corey Knebel, inserted in the eighth to protect a 2-1 lead, threw a wild pitch that allowed Mayfield to escape up to third.
Fellow Sooner senior captain Max White made due of that, placing an RBI single into right center.
That notched things up, and moments after first baseman Matt Oberste fanned, designated hitter Kolbey Carpenter singled and second baseman Hector Lorenzana hammered a go-ahead, two-run double to left center.
OU closer Jacob Evans did the rest, tossing a pair of scoreless innings while striking out a couple and surrendering just one hit to pick up his fifth save of the season.
In doing so, he enabled OU to win its first series over Texas since 1998 and the first in Austin since 1997.
The Sooners took an early 1-0 lead in the top of the second when Carpenter raced home and scored courtesy of one of Texas' two errors in the frame.
But that lead was short-lived, as the Longhorns captured their first lead in the third on third baseman Erich Weiss' two-run double to the wall in left center.
They kept that lead for four-plus frames until OU got busy late.
Sooner starter Adam Choplick lasted just 2 2/3 innings, striking out five and walking three to go around two hits that helped account for two unearned runs.
Longhorn starter Nathan Thornhill distanced much further in the contest, going seven innings without an earned run—his only blemish was that unearned run in the second—while striking out seven Sooner hitters to no walks and four hits.
OU (27-6, 7-2 Big 12) gets back to action with another road series, this time against the Baylor Bears in Waco, Texas, with first pitch slated for 6:35 p.m. CT Friday.