With a 13-2 record in conference play, the Sooners (45-4) need just one win in the final two games to capture their sixth regular season title under head coach Patty Gasso, adding to the four conference tournament titles they've also won.
Senior Keilani Ricketts hit a grand slam in a six-run third inning, while sophomores Lauren Chamberlain and Shelby Pendley each hit solo shots and junior Brittany Williams added a two-run blast in the fifth.
The four home runs were the most hit by OU since hitting five in game two of a doubleheader at Wichita State on March 27.
Ricketts was the beneficiary of the offensive outburst as she ran her record to 26-1. The lefthander allowed one run on three hits and a walk while striking out five.
Oklahoma State used a two-out triple and RBI single in the first inning to hold a 1-0 lead going into the third, but the Sooners took advantage of a pair of OSU miscues to take a 6-1 lead.
Sophomore Callie Parsons led off the inning by reaching on an error as her grounder went through the legs of shortstop Gessenia DeLaCruz. Senior Brianna Turang followed with a grounder of her own to DeLaCruz, but, in trying to force out Parsons at second base, DeLaCruz's throw was off the mark and ran all the way to the wall in right field.
Tied at 1-1 and with Turang on third following the error, Chamberlain delivered by lacing a single back up the middle to drive home what would turn out to be the winning run.
Sophomore Georgia Casey followed Chamberlain with a bunt single, while a walk to Pendley loaded the bases for Ricketts. On a 1-2 pitch, Ricketts sent a shot over the wall in center field for her fifth career grand slam and her second this season.
The homer, which put the Sooners up 6-1, was Ricketts' 12th this season and 47th of her career, giving her sole possession of fifth place in OU annals and a tie for eighth on the Big 12 list.
Chamberlain came up again in the fourth inning and, with two outs, turned on a full-count pitch for a solo home run to left. It was No. 23 on the season and No. 53 in her career.
Her single-season total is second-best in the Oklahoma history books and third best in the Big 12. Her career figure keeps her third at Oklahoma and moves her into fifth on the conference ledger.
Two more home runs in the fifth inning gave the Sooners their 20th run-rule victory of the season.
Pendley was the first batter to face relief pitcher Simone Freeman, who replaced Kat Espinosa after the OSU starter threw the first four innings and allowed seven runs - five earned - on four hits and three walks with five strikeouts. Pendley worked the count to 3-0 before unleashing a blast to right field.
It was Pendley's 19th home run this season, tying for sixth on OU's single-season list.
Two batters later, senior Jessica Shults singled up the middle and Williams came through with a two-run home run to center field to make it 10-1 in Oklahoma's favor. It was Williams' sixth home run this season and the 24th of her career.
The series shifts to Norman on Saturday. First pitch is scheduled for noon and the game will be shown on Fox Sports Network.