The PGA pair captured the $10 million top prize and tour bragging rights over the Saudi-backed upstart circuit in the four-man event at Shadow Creek in Las Vegas.
"We're super happy to get the win. It's a nice way to finish the year," McIlroy said. "Scottie and I got off to a pretty good start and then from there it was just about trying to keep the momentum."
The event, played mostly after dark under special lighting, pitted four-time major winner McIlroy and two-time Masters champion Scheffler against five-time major winner Koepka and two-time US Open champion DeChambeau.
"Under the lights was fun," Scheffler said. "It was really challenging."
The Showdown joined the majors as one of the few places where top players from the rival tours tested each other since the start of LIV, whose Saudi Arabian Public Investment Fund backers remain in talks with the PGA about reuniting.
"It was great. I'd love to have another opportunity. Felt like it was a pillow fight from us," DeChambeau said.
"It's good for the fans," added Koepka. "We didn't play that good but they played really solid."
The Showdown featured a best-ball format for the duos on the first six holes, an alternate shot format on the second six and a singles format over holes 13 to 18 with McIlroy facing DeChambeau and Koepka against Scheffler for one point each.
Northern Ireland's McIlroy, who last month captured his sixth Race to Dubai crown on the DP World Tour, won the first two holes with five-foot birdie putts.
McIlroy sank a 40-foot eagle putt and won the fourth hole when DeChambeau missed an eagle putt from inside five feet, giving the PGA duo a 3&2 best-ball triumph for the first point.
"Rory getting off to a great start was pretty big for our team and made a statement out of the gate," said Scheffler.
Scheffler gets clincher
Alternate shot began under the lights with Scheffler and McIlroy winning the par-4 ninth to go 1-up.
PGA Player of the Year Scheffler, whose nine wins this year include a second Masters title and Paris Olympic gold, dropped his approach six feet from the hole and the birdie was given after the LIV duo couldn't make par.
Koepka, last year's PGA Championship winner, sank an eight-foot birdie putt at the 11th to lift LIV level in the format entering the last hole.
"It was nice to make one," Koepka said. "I felt like we needed it."
McIlroy, however, responded with a six-foot birdie putt to win the 12th and give the PGA a 2-0 advantage, leaving LIV in need of two singles wins to force a playoff.
"It was a bit of a battle in the alternate shot and we were lucky to scrape a win," McIlroy said.
McIlroy sank a five-foot par putt to win the par-3 13th after DeChambeau, who edged McIlroy on the final hole to win the US Open in June, lipped out his par putt.
Scheffler also parred to win 13 for a 1-up lead over Koepka.
McIlroy sank a 15-foot birdie putt to win 14 for a 2-up edge while Koepka made an eight-footer for birdie to win 14 and tie Scheffler.
At 15, McIlroy missed a bogey putt to hand DeChambeau his first hole and Koepka missed a par putt give Scheffler a 1-up lead.
On the par-5 16th, both LIV players went into the trees off the tee and Scheffler delivered the clinching blow with a tap-in birdie, sealing a Showdown-clinching half-point by going 2-up with two holes to play after Koepka missed a 14-foot birdie putt.
