With the move on Sunday, the team is letting go of a pitcher who started 49 games over the 2021 and '22 seasons and was in the rotation on Opening Day this season.
In a corresponding transaction, the Guardians activated right-hander Triston McKenzie from the 60-day injured list to make his season debut in Sunday's game against the Minnesota Twins in Minneapolis.
McKenzie tossed five scoreless innings Sunday, striking out 10 Twins and allowing only one baserunner, a two-out single by Michael Taylor in the third inning. The 25-year-old right-hander threw 79 pitches in the Guardians' 2-1 victory.
Plesac, 28, went 1-1 with a 7.59 ERA in five starts this season. The right-hander is 26-27 with a 4.20 ERA in 84 career games (83 starts) with Cleveland.
At Columbus, he started five games with a 1-3 record and 7.56 ERA.
Also on Sunday, the Guardians optioned Michael Kelly to Triple-A Columbus.
Kelly, 30, had yet to pitch for the Guardians this season. He recorded a 2.25 ERA without a decision in four relief appearances with the Philadelphia Phillies in 2022.
McKenzie was shut down a couple of days before the start of the season after an MRI revealed a strain in his right teres major muscle. He made his final rehab start Tuesday but was limited to 43 pitches because of a rain delay.
McKenzie, 25, went 11-11 for the Guardians last season with a 2.96 ERA, ninth best in the American League. He is 18-21 with a 3.68 ERA in 64 career games (60 starts) with Cleveland.
Reuters and The Associated Press contributed to this report.