On July 6, 2019, the Rangers selected Payano's contract and promoted him to the major leagues.[9] He made his debut that day, pitching a scoreless inning in relief.[10] In 2019, Payano produced a 1–2 record with a 5.73 ERA in 22 MLB innings. Payano was designated for assignment on September 1 and was outrighted to Nashville on September 3.[11] He elected free agency following the season on November 4.[12]
New York Mets
On December 12, 2019, Payano signed a minor league contract with the New York Mets organization.[13] He did not play in a game in 2020 due to the cancellation of the minor league season because of the COVID-19 pandemic.[14] Payano was released on September 5, 2020.
Detroit Tigers
On February 8, 2021, Payano signed a minor league contract with the Detroit Tigers organization.[15] Payano made 25 appearances (24 starts) between the Double-A Erie SeaWolves and the Triple-A Toledo Mud Hens, registering a cumulative 8–8 record and 4.65 ERA with 117 strikeouts in 124.0 innings pitched. He elected free agency following the season on November 7.[16]
Cincinnati Reds
On February 1, 2022, Payano signed a minor league contract with the Cincinnati Reds.[17] Payano pitched in 50 games for the Triple-A Louisville Bats, posting a 2–4 record and 3.26 ERA with 62 strikeouts in 60+2⁄3 innings of work. He elected free agency following the season on November 10.[18]
On July 6, 2023, Payano's contract was purchased by the Leones de Yucatán of the Mexican League.[19] In 5 appearances down the stretch, he recorded a 5.79 ERA with 5 strikeouts across 4+2⁄3 innings pitched.
Payano made 14 appearances for the Leones in 2024, struggling to an 8.76 ERA with 10 strikeouts across 12+1⁄3 innings of work. He was released by Yucatán on June 16, 2024.[20]
Tigres de Quintana Roo
On June 24, 2024, Payano signed with the Tigres de Quintana Roo of the Mexican League.[21] In 18 appearances for the Tigres, he posted a 1–0 record and 3.06 ERA with 15 strikeouts across 17+2⁄3 innings pitched.