Arenado went 1 for 3 with three RBIs in the 6-5 win Monday at Busch Stadium in St. Louis.
Veteran pitcher Adam Wainwright allowed seven hits and five runs in 5 2/3 innings to earn in his first win of the season.
Tyler O'Neal smacked a third-inning RBI double for the go-ahead run in the bottom of the third inning.
The Cardinals bullpen did not allow a hit or a run over the final 3 1/3 innings.
Wainwright got the Mets out in order in the top of the first inning. Second baseman Tommy Edman hit a leadoff triple for the Cardinals in the bottom of the inning.
Dylan Carlson scored Edman in the next at-bat with a sacrifice fly to right field.
Wainwright ran into trouble in the next inning. The Cardinals pitcher allowed a Pete Alonso double in his first exchange. He struck out Dominic Smith in the next at-bat.
Wainwright struck out pitcher Joey Lucchesi for the second out of the inning, but walked Jeff McNeil in the next at-bat to bring in Pillar from third base.
Lucchesi returned to the mound in the bottom of the inning. He got outs from Paul DeJong and O'Neill to start the frame. Harrison Bader stepped into the box for the next at-bat.
Bader took a called strike for the first pitch of the exchange. He then worked ahead in the count and smashed a 3-1 cutter to left field for his second home run of the season.
Bader's blast traveled an estimated 450 feet with an exit velocity of 109 mph, according to Statcast. The solo shot tied the game at 2-2.
Smith gave the Mets a 3-2 lead with an RBI ground out in the top of the next inning. Pillar smacked a 414-foot, two-run homer in the next at-bat to give the Mets a 5-2 edge.
The Cardinals rallied in the bottom of the inning to take control of the game.
Lucchesi got outs from Wainwright and Edman to start the frame. He allowed back-to-back singles to Carlson and Goldschmidt in the next two at-bats.
Arenado walked to the plate for the sixth at-bat of the frame. The Cardinals third baseman fell behind 1-2 in the count. He fouled off the next three pitches. Arenado hit the seventh offering of the exchange over the left field fence.
Arenado's 383-foot blast tied the game at 5-5. DeJong doubled in the next at-bat. O'Neil plated the Cardinals shortstop with his double one pitch later.
Edman and DeJong each went 2 for 4 with a run scored in the win.
Pillar went 2 for 4 with two RBIs and two runs scored in the loss. Alonso went 3 for 4 with two runs scored for the Mets.
Lucchesi allowed seven hits and six runs in 2 2/3 innings to drop to 0-2 this season.
The Cardinals (17-12) host the Mets (11-12) at 7:45 p.m. EDT Tuesday at Busch Stadium. Mets ace Jacob deGrom battles fellow right-handed pitcher Johan Oviedo in the second game of the series.