In Matz's first start since undergoing elbow surgery last August, he gave up two solo homers and was pulled after four innings and 89 pitches in a 5-1 loss to St. Louis last Sunday.
"He just battled himself all (day)," Mets manager Mickey Callaway told Newsday. "He wasn't finishing at times and just didn't look like he had the confidence to throw it over."
Washington's No. 3 starter, left-hander Gio Gonzalez (1-0, 1.50), was sharp in his first outing, holding Cincinnati to one run, five hits and a walk with seven strikeouts through six innings.
Gonzalez is coming off a bounce-back 2017 season when he lowered his ERA from 4.57 in 2016 to 2.57 and won 15 games.
He is 14-5 with a 2.93 ERA and one shutout in 23 starts against the Mets, including 3-0 with a 2.25 ERA last season.
Matz is 1-2 with a 2.17 ERA in four career starts against the Nationals.
On Thursday, the Mets used three homers and a solid effort from Jacob deGrom (2-0) to ruin the Nationals' home opener, giving Washington its third straight loss on a day they announced president of baseball operations Mike Rizzo signed a two-year extension through 2020.
Yoenis Cespedes, Michael Conforto and Jay Bruce (seventh-inning grand slam) homered for New York.
"Any time you can come in and beat a team of this caliber is huge," Bruce told MLB.com. "It's going to be like this all year. There's going to be big series. I hope to continue playing in them and have them mean something every time we play.
"Everyone in here's goal is to be playing meaningful baseball when we get to September, and to do that, we've got to beat these guys."
Conforto's home run came in his second at-bat after returning from the disabled list following left shoulder injury. He had not played since Aug. 24.
"What I think he does is add a whole other level of anxiety for the other team," Callaway told the New York Post. "As a guy who was a pitching coach, when you're preparing for a team, you have to pay attention to a guy like him."
The Mets' bullpen tossed three scoreless innings and has a 1.27 ERA thus far.
Nationals starter Stephen Strasburg (1-1) allowed four runs and five hits with six strikeouts and two walks in six innings, surrendering the Conforto and Cespedes homers.
"I know mistakes were made, and I paid the price for it," Strasburg told The Washington Post. "Sometimes you get away with them. But this time I didn't."
Adam Eaton continued his torrid start for Washington (4-3), opening the game with a double and scoring the game's first run. In the third, he walked and scored. He has reached base in each of his first six games while going 10--for-22 (.455).
After Eaton dislodged some scar tissue in his left ankle on a third-inning slide, he left the game in the sixth inning, but is not expected to miss much time after x-rays were negative.
"They don't think (it's) anything major," Eaton told The Washington Post. "It's like a day or so for it to realign itself and be good."
Third baseman Anthony Rendon had his first multi-hit game of the season Thursday, going 3-for-3 with two doubles, and has hit safely in all seven games.
Rendon is 3-for-12 in his career against Matz, and Michael A. Taylor is 3-for-10 with a home run.
Mets outfielder Juan Lagares is 16-for-43 with a homer and five RBIs against Gonzalez, and Cespedes is 7-for-13 with two homers and Jose Reyes is 7-for-19.