Senay also had five RBIs in a decisive regional game last year against Vanderbilt.
The top-seeded Wolfpack (47-14) beat the third-seeded Tribe (39-24) for the second straight night and went 3-0 in the regional. Last year, N.C. State had to climb through the losers' bracket after losing its second game.
"I'm not going to say it was easy because every team was good and this regional was tough," Senay said. "But winning three straight was definitely a lot easier (path) than last year."
Jake Fincher and Logan Ratledge both had three hits and an RBI to help N.C. State reach the super regionals for the third time since 2008. The Wolfpack will face the winner of the regional hosted by Oregon.
The Tribe's Jackson Shaver hit an RBI double in the seventh to snap the N.C. State pitching staff's string of 22 2-3 straight scoreless innings — which began in the second inning of Friday night's 4-1 win over Binghamton.
Matt Wainman (4-4) allowed six runs and 10 hits in 5 1-3 innings for William & Mary. The Wolfpack wasted no time pouncing on him.
Trea Turner and Fincher led off with consecutive singles to center field. Senay made it 3-0 by driving a 2-0 pitch well over the wall in right field for his team-leading eighth homer and second of the regional.
"Once Tarran hit that ball, I would say a little relief came off our shoulders," Turner said.
N.C. State added three more runs in the sixth. Fincher's two-out single to third base scored Matt Bergquist. Logan Ratledge followed him around on the play and was tagged out at the plate but was ruled safe due to obstruction.
Freshman Brad Stone (3-2) became the second N.C. State lefthander to beat the Tribe — this one coming less than 24 hours after ace Carlos Rodon threw a two-hitter with 10 strikeouts in a 1-0 win.
Stone allowed four hits in 5 1-3 innings for his first victory since beating Maryland on March 31.
"They were the best team here in this regional and they played like the best team," Tribe coach Jamie Pinzino said. "Their pitchers did a good job two days in a row of shutting down our offense."
Grant Sasser struck out three of the five batters he faced for his eighth save.
Turner made the defensive play of the night at shortstop in the sixth, diving to his right to field Michael Katz's sharp grounder in the hole and firing a strike to first base to retire him.
Not that everything was clean in the field for the Wolfpack as three errors in the eighth led to the Tribe's second run.