The 38-year-old Byrd, who tested positive for the growth hormone secretagogue Ipamorelin, accepted responsibility and will not appeal. He also was suspended for 50 games in 2012 after testing positive for Taxoxifen.
The suspension begins immediately.
Byrd joined the Indians before the 2016 season after signing a minor league contract. He made the major league team out of spring training and was batting .270 with five home runs and 19 RBIs.
The PED suspension was the second to hit Indians outfielders this year. Before the season, Abraham Almonte drew an 80-game suspension after a positive test for the performance-enhancing drug Boldenone.
Byrd's first suspension in 2012 came after he said he used Taxoxifen on a physician's advice after surgery.
"Since that time, I have paid close attention to the substances that are banned by the Joint Drug Agreement, as I had no intention of taking any banned substances," Byrd said. "I relied upon a medical professional for assistance and advice with respect to the supplements that I was taking. However, certain supplements I was taking were not on the NSF Certified for Sport list, and therefore, I assumed certain risks in taking them.
"When I learned that I had tested positive for Ipamorelin, I retained the services of private counsel and an independent chemist to determine the origin of the Ipamorelin test result because I never knowingly ingested Ipamorelin. After an extensive investigation by my lawyers and an independent chemist, it was concluded that the most likely source of Ipamorelin was a tainted supplement.
"I alone am responsible for what I put in my body, and therefore, I have decided for forgo my right to an appeal in this matter and accept the suspension. I apologize for any harm this has caused the Cleveland Indians, Indians' fans, my teammates, and most importantly, my family."
Byrd spent last season with the Cincinnati Reds and the San Francisco Giants, batting a combined .247 with 23 home runs and 73 RBIs in 135 games. He started his major league career with the Philadelphia Phillies in 2002 and has 159 career homers with 10 different teams in 15 seasons.