On April 18, Syndergaard made his third start of the season against the Phillies at Citizens Bank Park pitching for his second win of the year going seven innings allowing one run, five hits, two walks and struck out eight. Through his first three starts, Syndergaard was 2–0 with a 0.90 ERA, 29 strikeouts and four walks in 20 innings. In concert with that he also threw at least eight strikeouts while allowing no more than one run in fall of his first three starts for the first such start of a season by a pitcher since Randy Johnson went four games with those stats in 1995. With those numbers, he now ranks second in Mets history with the most strikeouts in first three starts of the season with twenty-nine surpassing Tom Seaver (1971 with 28), Nolan Ryan (1970 with 28) and behind Pedro Martínez with thirty in 2005.

For the second straight season, Syndergaard was chosen to start on Opening Day. He pitched 6 innings, striking out 10 batters, becoming the second Met, after Pedro Martinez in 2005, to register 10 or more strikeouts on Opening Day. He was placed on the disabled list at the end of May and was activated on July 12, after missing the whole month of June with a strained ligament in his right index finger. On July 22, he was again placed on the disabled list after contracting hand, foot and mouth disease, and returned on August 1. He threw the first complete game of his career on September 2, striking out 11 batters in a 4–1 victory over the San Francisco Giants at AT&T Park. He pitched on the last day of the season, throwing his first shutout in a complete game to defeat the Miami Marlins by a score of 1-0 at Citi Field. For the season, he was 13-4, with a 3.04 ERA. He led the major leagues in stolen bases given up, with 32 (as only three runners were caught stealing).

In 2011, Syndergaard pitched for the Bluefield Blue Jays of the Rookie-level Appalachian League, the Vancouver Canadians of the Class A-Short Season Northwest League, and the Lansing Lugnuts of the Class A Midwest League. Pitching for the three teams, he was 5-2 with a 1.83 ERA, and 68 strikeouts in 59 innings, as runners stole 19 bases against him in 23 attempts.

Before the 2012 season, MLB.com rated him as the 95th-best prospect in baseball. He pitched alongside highly touted Blue Jays prospects Justin Nicolino and Aaron Sanchez in the minor leagues. The pitchers were together known as the “Vancouver Trio” and the “Lansing Trio” when they played for the Canadians and Lugnuts respectively. He pitched for Lansing in 2012, and appeared in the Midwest League All-Star Game. Pitching for Lansing, he was 8-5 with a 2.60 ERA, and 122 strikeouts in 103.2 innings.

On December 17, 2012, the Blue Jays traded Syndergaard, Travis d’Arnaud, John Buck and Wuilmer Becerra to the New York Mets for R.A. Dickey, Josh Thole and Mike Nickeas. At the time of the trade, Syndergaard and d’Arnaud were two of the Blue Jays’ top three prospects, and Dickey was the reigning winner of the Cy Young Award for the National League.

In 2014, Syndergaard pitched for the Las Vegas 51s of the Class AAA Pacific Coast League, where he had a 9–7 win–loss record, a 4.60 earned run average (ERA), and 145 strikeouts, which led the league in 133 innings. The Mets decided not to promote Syndergaard to the major leagues as part of its September call-ups. Syndergaard began the 2015 season with Las Vegas, pitching to a 3–0 record with a 1.82 ERA, and 34 strikeouts in 29.2 innings.

The 6-foot-6 right-hander throws from an overhand delivery. PITCHf/x data shows him throwing two fastballs (four-seam, sinker) at 95–99 miles per hour (153–159 km/h), while topping out at 101 mph, along with a curveball between 80–84 miles per hour (129–135 km/h), a changeup, and a slider at 88–94 miles per hour (142–151 km/h). He added the slider to his repertoire during his first season in the majors. He initially began working with it to increase the spin on his curveball, saying in July 2015, “As of now, I’m just a fastball / curveball / changeup guy.” However, by that year’s postseason, he was using the pitch with regularity, throwing 17 in his first playoff appearance.

For the 2016 season, he was 14-9 and led the majors in lowest home runs per nine innings (0.54). He led all major league pitchers with an average fastball velocity of 98.0 miles per hour. He led the major leagues in stolen bases given up, with 48 (18 ahead of Jimmy Nelson; as only nine runners were caught stealing). He started the 2016 NL Wild Card Game and pitched seven shutout innings, but the Mets lost to the San Francisco Giants.

Beginning in 2016, Syndergaard altered his windup to minimize movement, resembling his motion when in the stretch.

Syndergaard started on Opening Day for the Mets in 2017. Against the Atlanta Braves, Syndergaard struck out seven over six innings and got a base hit in a 6–0 Mets victory. He left the game early due to a blister on his middle finger which caused him to get a no decision. On April 30, Syndergaard left the game after experiencing tightness in his right biceps. The next day, on May 1, he was placed on the 10-day disabled list due to a torn lat muscle in his right arm. He was transferred to the 60-day disabled list on May 7.

Syndergaard is a weightlifting enthusiast and is capable of squatting 455 pounds (206 kg) and deadlifting 512 pounds (232 kg). After he shared a photo of himself weight training while dressed as the superhero Thor, due to the similarity between his last name and the fictional location Asgard, he acquired the nickname “Thor”. Syndergaard has embraced the nickname; his mother has an Australian Shepherd named Thor and Syndergaard has “Thor” stitched into one of his gloves. Syndergaard has taken to naming all of his gloves after fictional characters. He has previously used gloves named “Drago” (after the Rocky IV character), “Heisenberg” (after the alias of a Breaking Bad character) and “Rick Grimes” (after The Walking Dead character). Syndergaard auctions his gloves off in order to raise money for the Sjögren’s Syndrome Foundation, which raises money to fight Sjögren’s disease, an autoimmune disease from which his mother suffers. In 2017 the Mets collaborated with Marvel Comics to put out a Noah Syndergaard as Thor bobblehead and held fan giveaways of the souvenir at games at Citi Field during the 2017 and 2018 seasons.

Syndergaard has made several appearances on television shows. In 2017, he made a cameo appearance in “The Spoils of War”, a Season 7 episode of Game of Thrones on HBO, in which he played an unnamed Lannister spearman in the episode’s climactic battle. Syndergaard appeared in a Season 1 episode of Kevin Can Wait, a sitcom starring Mets fan Kevin James, in which he played a man wearing a viking costume for Halloween. He voiced himself in a baseball-themed episode of the animated series Uncle Grandpa alongside fellow MLB players Chris Archer, Adam Jones, José Altuve, and David Price. He also appeared as himself in a segment of the prank reality program Impractical Jokers featuring Joe Gatto.

On May 2, 2019, Syndergaard threw a complete game shutout against the Cincinnati Reds, allowing four hits and striking out ten batters, and hit a solo home run for the Mets’ only run. He was the first pitcher since Bob Welch in 1983 to throw a shutout and hit a home run in a 1–0 win. For the performance, he was named National League Player of the Week for the week of April 29 to May 5. Syndergaard again won National League Player of the Week honors for the week of July 29 to August 4, after starts against the Chicago White Sox and Pittsburgh Pirates.

On March 24, 2020, Syndergaard was diagnosed with a torn UCL in his right elbow and underwent Tommy John surgery on March 26, putting him out for the entire 2020 season.