Reigning Masters champion Scheffler, who won the Players Championship earlier this month, birdied five of his last six holes to beat Australian Jason Day 2&1 at Austin Country Club.
"It was a tough match," Scheffler said. "Jason came out of the gates really hot."
Four-time major winner McIlroy took his only lead of the match with a 12-foot birdie putt on the 18th hole to defeat Tokyo Olympic champion Xander Schauffele 1 up on the Texas layout.
"I needed to dig deep," McIlroy said. "I got down early but I battled back."
Scheffler will face pal Sam Burns in an all-American semi-final on Sunday morning while McIlroy, the 2015 WGC Match Play winner from Northern Ireland, will face American Cam Young in the other. The winners meet Sunday afternoon for the title.
Burns beat Canada's Mackenzie Hughes 3&2 while 2022 British Open runner-up Young defeated compatriot Kurt Kitayama 1 up.
Scheffler, who won three of the last four holes to edge J.T. Poston 1 up in the morning round of 16, made another fightback to dispatch Day, the 2014 and 2016 Match Play winner.
Day won the fourth and fifth holes with birdies and eagled the sixth from just inside six feet to go 3 up, the biggest deficit for Scheffler this week.
Scheffler won the eighth on a Day bogey and the ninth on a 29-foot birdie putt then two-putted from 48 feet for birdie to win the par-5 12th and pull level.
"I just stayed patient," Scheffler said. "He made a mistake on eight and then I birdied nine and it was a match from there on."
Scheffler drove the green at the par-4 13th and tapped in for birdie to win the hole and seize his first lead, then went 2 up when Day made a bogey to lose 14. Both birdied 15 and 16 and Scheffler's tee shot at the par-3 17th ended two inches from the hole to seal a date with Burns.
"Should be a fun match. We'll have a good time out there," Scheffler said. "Should be a good challenge for both of us."
Schauffele sank an 18-foot birdie putt to win the first hole. McIlroy, who edged Aussie Lucas Herbert 2 up in the morning, and Schauffele each won two more holes with birdies on the front nine.
"I'm 16-under for the two rounds of golf I've played today," McIlroy said. "It just sort of shows you the calibre you need to play at to compete out here."
McIlroy sank a nine-foot birdie putt to win the 10th and level the match then tied 11 on a par putt from nearly eight feet.
Schauffele birdied to win the par-5 12th but plunked his tee shot into the water to drop the 13th and fall level again, which is how they stayed until McIlroy's closing putt.
"It's exciting," he said. "I went back and regrouped after (missing the cut at) the Players and worked on a couple of things and it's so nice to feel that work last week pay off this week."
Burns, Young led early
Burns, who earlier ousted fourth seed Patrick Cantlay 2&1, lost the first two holes on Hughes birdies but birdied to win the fourth and fifth and sank a 51-foot birdie putt to win the par-3 seventh and grab the lead. Hughes never pulled level again.
Young, chasing his first PGA title, sank a 40-foot birdie putt to win the ninth hole and seize a 3-up lead.
Young was two inches from an ace at the par-3 11th but Kitayama made a 10-foot birdie putt to tie the hole. Kitayama won 13 and 14 with birdies to tighten the match but never got level again.
