The Sooners fell 3-0 in Friday night's opener in front of 9,158 at OneOK Field.
OSU ace Andrew Heaney kept the Sooner hitters off balance all night en route to throwing his Big 12 leading fourth complete game, and OU just never really had an answer for him.
Heaney struck out seven, walked just one and allowed only three hits all night in his third shutout of the year.
"Andrew Heaney is really tough," said OU head coach Sunny Golloway. "It comes back to us having discipline at the plate. We offered at too many pitches out of the zone."
Still, credit has to be given where credit is due.
They did so in the top of the third on a pair of RBI singles by second baseman Robbie Rea and catcher Jared Womack.
Shortstop Hunter Bailey plated the game's final run on an RBI single in the bottom of the fifth, making it 3-0.
John, despite throwing his fourth complete game of the season, was tagged with the hard luck loss after giving up three earned runs on seven hits.
He struck out five.
Center fielder Max White extended his hitting streak to 10 games, going 1-for-2 with a walk.
OU and OSU get back to action in game two at 7 p.m. Saturday as the series shifts to Oklahoma City's Chickasaw Bricktown Ballpark. The series finale is set for 4 p.m. Sunday.