The Sooners (48-4) scored eight runs in the first inning, and then followed it up two innings later with another eight-spot in the third to break the game open early.
"We've been waiting for this moment for a while," OU head coach Patty Gasso said. "The team was ready to come out and attack early, which is exactly what we did, so everybody followed the game plan to a T."
The victory, which is the team's 21st via run-rule this year, earns Oklahoma a date with Arkansas on Saturday at 1 p.m. The Razorbacks advanced to the winner's bracket following a 5-1 win over Fordham in the first game of the Regional.
Sophomore infielder Lauren Chamberlain led an OU offense that got 13 hits from seven different batters. Chamberlain was 3-4 with two runs scored and five runs batted in, including three on a first-inning home run.
"If you look down our lineup you see that everybody had some kind of offensive contribution, which is very important from the top to the bottom," Gasso said. "I love the way Brittney Williams swung today, very authoritative and hard-hitting. [Destinee] Martinez again did her job. [Brianna] Turang again doing her job. [Callie] Parsons laid down the squeeze, so we're trying to show you a little of everything.
"If you want to play us up we're going to hit it by you. If you want to play us deep we're going to drop down and squeeze. We just try to keep you guessing throughout the game."
After a 1-2-3 top of the first, Oklahoma broke the game open in the bottom of the frame on five hits and a pair of Marist errors. It improved OU's record to 28-0 when scoring in the opening inning and 44-0 when scoring first.
Chamberlain led things off with a single and moved to third when sophomore Georgia Casey doubled to extend her hit streak to a career-best 12 games. A walk to fellow sophomore Shelby Pendley loaded the bases for senior Keilani Ricketts. She pulled a single through the right side to score Chamberlain and Casey, and the ball deflected off Casey as she came home to enable Pendley to finish clearing the bases.
Ahead 3-0, Ricketts took third on a ground out and scored when the Red Foxes left fielder Christina Lausch dropped a fly ball from junior Brittany Williams, who reached second on the play.
The Sooners then used some small ball as junior Destinee Martinez reached on a bunt single and moved Williams to third, while sophomore Callie Parsons batted next and executed a squeeze bunt to score Williams and make it 5-0.
Two batters later, Chamberlain came to the plate for the second time in the inning and launched a three-run home run to left center. It was her 26th this season and 56th of her career, tying former Sooner Amber Flores for second on OU's career list.
In addition, Chamberlain scored her 71st run of the season on the homer, tying Norrelle Dickson for the school single-season record, set in 2006.
Oklahoma scored one run in the second when Martinez lifted a sacrifice fly to center field to score Ricketts, who had walked and reached third on a double by Williams.
Oklahoma's second eight-run inning of the ball game brought the score to 17-0 after three innings.
With one out and Turang on first, Casey singled to left before a walk to Pendley loaded the bases. Ricketts then drew a bases-loaded walk to score Turang before senior Jessica Shults singled back up the middle to drive home two and make it 12-0.
The bases were loaded again when Williams singled. Martinez followed with an RBI single and Parsons walked to push across two more runs. A chopped single to second base from Turang plated another run, while Chamberlain tallied her third hit of the game with a double off the wall in left field that scored two and brought the game to its final margin.
The offensive support was more than enough for Ricketts and fellow senior Michelle Gascoigne. Ricketts, who won to improve to 28-1, allowed just one hit while striking out seven. She then yielded to Gascoigne who pitched the final two innings with two walks and five strikeouts.