Plesac will start Thursday night against the Kansas City Royals as the Indians try to end a nine-game losing streak - the club's longest since 2012.
Manager Terry Francona said the plan is for Plesac to throw "60ish" pitches in his first outing as he builds up arm strength. Plesac recently completed a rehab stint at Double-A Akron and is itching to help the slumping Indians.
"He has been exemplary in his work, which is not surprising," Francona said. "We've had people from other teams come to us and say, you know, watching this kid on the field, man, wow, that's pretty special what he's doing.
"So that makes us proud. And we knew he wanted to pitch right away for us. I think we have an obligation though to make sure that guys can compete with health and not hurt themselves, so there was a reason we had him go twice (at Akron)."
To make room for Plesac, the Indians optioned right-hander J.C. Mejia to Triple-A Columbus.
The return of the 26-year-old Plesac is a much-needed boost to the Indians, who are still missing top starters Shane Bieber (shoulder) and Aaron Civale (finger). They aren't supposed to be back for several more weeks.
Cleveland has also had several other key players out with injuries, the latest outfielder Eddie Rosario. He went on the injured list Wednesday with a strained right abdominal muscle.
Plesac last pitched for the Indians on May 23 at Minnesota. After giving up five runs in 3 2/3 innings, he aggressively yanked off his shirt and injured his thumb. Plesac described the incident recently as a "weird series of events."
He's 4-3 with a 4.14 ERA in 10 starts.