No. 1 Wake Forest and 10 other national seeds won their openers in the NCAA regionals on Friday before Penn began a late-night flurry of upsets.
The Quakers gave the Ivy League its first national tournament win over a Southeastern Conference opponent, beating No. 13 Auburn 6-3 in 11 innings.
Next, Oral Roberts took down No. 11 Oklahoma State 6-4 for its third win over the Cowboys this season and its nation-best 19th straight victory.
Minutes later, Rider finished an 11-10 win over No. 10 Coastal Carolina when Richie Sica made a diving catch of Caden Bodine's flare to center with the bases loaded.
Penn, which hadn't won in the tournament since 1990, took the lead on Ryan Taylor's double and added two insurance runs on consecutive squeeze plays. Four pitchers limited Auburn to four hits and struck out 14.
The Ivy League had been 0-9 all-time against the SEC in the tournament. Now Penn will try to make a run like conference made Columbia did last season, when it reached a regional final as a No. 3 regional seed.
Oral Roberts of the Summit League never trailed against the Big 12's Cowboys while winning its NCAA opener as a No. 4 regional seed for the third time. The Golden Eagles beat Wichita State in 2002 and Baylor in 2012.
Rider, from the Metro Atlantic Athletic Conference, got four RBIs from Jack Winsett and survived despite four pitchers allowing 14 hits and walking eight. The Broncs had lost 15 straight in the tournament since 1987.
Wake Forest posted its nation-leading 10th shutout with its 12-0 victory over George Mason. Seth Keener and two relievers combined on a three-hitter and Justin Johnson homered twice and drove in six runs.
The Southeastern Conference, which has 10 teams in the tournament, was 7-1 with Alabama and Texas A&M still playing Friday night. The Atlantic Coast Conference was 6-2.
Indiana State, seeded 14th and hosting a regional for the first time, got a scare from Wright State before winning 6-5.
The Sycamores of the Missouri Valley Conference trailed until they got to Horizon League pitcher of the year Sebastian Gongora in the eighth. Tristan Haught, who came on with one out and two runners on, gave up a sacrifice fly and walked two straight before Grant Magill singled in two runs for the lead.
"That wasn't the way we drew it out, by any means," Sycamores coach Mitch Hannahs said. "It wasn't the prettiest, but it worked out. I told our club we didn't play real well but sometimes toughness, fight and resiliency trumps that, and I thought that's what happened today."
Six No. 3 regional seeds won - Washington, Texas Tech, North Carolina State, Samford, Troy and Indiana.
LSU rides Crews, Skenes: LSU's Dylan Crews and Paul Skenes performed like guys projected to be the top two picks in the amateur draft.
Crews was 3 for 5 with a double and an RBI in the Tigers' 7-2 win over Tulane. Skenes scattered seven hits, walked none and struck out 12 in his first complete game.
Skenes also made one of the defensive plays of the day when he caught James Agabedis III's line drive between his legs and threw to first to double off the runner.
"I got tired of them hitting the ball up the middle," a grinning Skenes said, "and I wanted to catch one."
100-RBI season: Maryland's Nick Lorusso became the first player in 20 years to drive in 100 runs in a season when he homered in the first inning in a 7-2 win over Northeastern. New Mexico State's Billy Becher was the previous player with 100 RBI in 2003.
Big bats: Duke's MJ Metz homered on three straight plate appearances in a 12-3 win over UNC-Wilmington. ... Billy Amick hit a grand slam to break open the game in the eighth and finished with five RBI in Clemson's 12-5 win over Lipscomb. ... Alex Vergara homered twice for Lipscomb. ... Kendall Diggs' bases-clearing single highlighted a five-run fourth inning in Arkansas' 13-6 win over Santa Clara. ... Dylan Campbell went 2 for 4 in Texas' 4-2 win over Louisiana and set the Big 12 record with his 36th straight game with a hit. ... Alberto Rios homered and had four RBI in Stanford's 13-2 win over San Jose State. ... Griffin Merritt and Christian Moore drove in three runs apiece to lead Tennessee past Charlotte 8-1.
Mound marvels: Four relievers combined to keep the Musketeers scoreless over the last five innings of Oregon's 5-4 win over Xavier. The Ducks' bullpen has a 1.44 ERA in five postseason games. ... Virginia had a no-hitter going in its 15-1 win over Army until Braden Golinski singled with one out in the seventh off Cullen McKay, who took over for Brian Edgington at the start of the sixth. ... Travis Smith and Mason Moore combined on a three-hitter in Kentucky's 4-0 win over Ball State, the Wildcats' first shutout in 31 all-time NCAA Tournament games. ... Iowa edged North Carolina 5-4 after closer Luke Llewellyn got two strikeouts to end the game with the tying run at third base.
Around the horn: Jim Jarvis' two-out RBI single gave Alabama its first walk-off victory of the season, 4-3 over Nicholls. ... Florida got a two-run homer from Josh Rivera in the first inning and six shutout innings from Jac Caglianone in a 3-0 win over Florida A&M. ... Virginia scored its most runs in an NCAA Tournament since 2016. The Cavaliers led 10-0 early and scored in all but two innings. ... Wright State's Andrew Patrick became the first Division I player this season to hit 20 homers and steal 30 bases. ... Arkansas has won eight consecutive regional openers since 2014. Wright State has lost all nine of its regional openers since 2006. ... Dallas Baptist's Ryan Johnson gave up eight earned runs in six innings against Washington, the most in his career. ... Edgardo Villegas and Yohandy Morales homered as Miami got out to a big lead early in a 9-1 win over Maine.