On July 21, 2019, the Padres selected Morejón's contract and promoted him to the major leagues.[9] He made his major league debut that day versus the Chicago Cubs.[10] In 2020, Morejón pitched to a 2–2 record and 4.66 ERA with 25 strikeouts in 19+1⁄3 innings across nine games (four games started).[11]
Morejón departed from a game started on April 11, 2021, against the Texas Rangers after suffering a left forearm strain. On April 20, it was announced that Morejón would undergo Tommy John surgery and miss the remainder of the 2021 season.[12] On April 23, Morejón was placed on the 60-day injured list.[13] After rehabilitating from his surgery, Morejón returned to the Padres' active roster on June 7, 2022.[14] He made a career–high 26 appearances for San Diego in 2022, logging a 5–1 record and 4.24 ERA with 28 strikeouts in 38.0 innings of work.[15]
On January 13, 2023, Morejón agreed to a one-year, $800K contract with the Padres, avoiding salary arbitration.[16] He was placed on the 60-day injured list to begin the season after suffering a left elbow sprain in spring training.[17] After a rehab assignment with Low–A Lake Elsinore, Morejòn was activated from the injured list on June 6 and optioned to Triple–A El Paso.[18]