[5] After signing, Sewald made his professional debut that same season with the Brooklyn Cyclones of the Low–A New York-Penn League where he was 0–2 with a 1.88 ERA in 28+2⁄3 relief innings pitched.

He pitched in the 2013 season with the Savannah Sand Gnats of the Single–A South Atlantic League,[6] compiling a 3–2 record and 1.77 ERA in 35 relief appearances.

During the season, he pitched for the United States national baseball team at the 2015 Pan American Games, earning a silver medal.

[11] He made his MLB debut the same day against the Miami Marlins at Citi Field and allowed two runs in a third of an inning.

[24] On July 31, 2023, the Mariners traded Sewald to the Arizona Diamondbacks for Ryan Bliss, Dominic Canzone, and Josh Rojas.

Sewald remained as Arizona's closer throughout their postseason run and pitched eight consecutive scoreless playoff appearances en route to the 2023 World Series.

[28] Sewald missed the beginning of the 2024 campaign with an oblique strain and pitched well after returning, going 11–for–11 in save opportunities and posting an 0.54 ERA.

On August 2, after multiple blown saves and an inflation of his ERA to 4.23, manager Torey Lovullo announced that Sewald would be removed from the closer's role.

[29] On January 22, 2025, Sewald signed a one-year, $7 million contract with the Cleveland Guardians including a mutual option for the 2026 season.

[30][31] Sewald's father, Mark, is a former college baseball pitcher[32] who was drafted out of high school by the Boston Red Sox in 1979.

[34] Sewald's younger brother, Johnny, an outfielder, was selected in the 14th round of the 2015 MLB draft out of Arizona State University by the Houston Astros.