The 16 runs are the most an OSU opponent has scored this season.
Cowboy starter Tyler Buffett (2-1) took the loss after giving up four hits and two earned runs in two innings.
Texas Tech designated hitter Adam Kirch hit two home runs, finishing 3-for-5 with six RBIs.
Andrew Rosa and Hunter Hagler both homered for OSU (21-10, 4-4 Big 12).
Reliever Corey Taylor (4-0) got the win for Texas Tech (24-10, 5-6). Taylor allowed six hits and four earned runs in two innings of work.
The Cowboys finish up the Big 12 series with the Red Raiders at 1 p.m. Sunday.