Mondesi went on the IL in March with a right oblique strain. He will bat seventh in the series opener against Tampa Bay.
Mondesi hit .256 with an AL-best 24 stolen bases in 59 games during the pandemic-shortened 2020 season.
The 25-year-old signed a one-year, $2,525,000 contract with Kansas City in the offseason to avoid arbitration as he has emerged as one of the young players the Royals are staking their rebuild around.
Kansas City has won four of its last five games and is third in the AL Central.
Information from The Associated Press was used in this report.