The 32-year-old deGrom left his outing after pitching three perfect innings. He struck out eight of the nine batters he faced and drove in a run with an RBI single in the second inning.
DeGrom tossed 51 pitches in his start and was replaced by Sean Reid-Foley.
In his previous start against the San Diego Padres on Friday, deGrom had to leave after six innings due to flexor tendinitis in his right arm.
The two-time National League Cy Young Award winner also was pulled May 9 against the Arizona Diamondbacks after five innings with right side tightness, which forced deGrom to miss his next two starts. On May 4, he was scratched from a start due to the same ailment.
DeGrom, a three-time MLB All-Star selection, lowered his ERA to 0.54 with his three shutout innings Wednesday. He has allowed just four earned runs this season, while his RBI against the Cubs gave him six on the year. He has a 6-2 record with 111 strikeouts over 67 innings.
The Mets went on to beat the Cubs 6-3 in the third game of the clubs' four-game series. New York also earned wins over Chicago on Monday and Tuesday.
The teams wrap up the series Thursday night at Citi Field.