Pena led the Tribe's Latin American scouting department since 2009.
"Over the course of the past month, Ramon and I have had numerous and extensive conversations about the future direction of our Latin American operations," Indians president of baseball operations Chris Antonetti said. "Based upon those discussions, we both felt that it would be best to part ways at this point.
"Ramon has made a great impact on the organization in his time with us. He's an outstanding and accomplished scout, executive and leader. We all wish Ramon the very best as he continues his distinguished career."
In a report on Baseball America, Pena added the the sides parted ways "in a mutual, friendly way.
"I want to thank the Dolan family for the opportunity they gave me to work for a fine organization like the Cleveland Indians," he was quoted as saying. "I enjoyed my time working with Chris Antonetti and [general manager] Mike Chernoff. I also enjoyed working with Mark Shapiro, who was responsible for bringing me to the Cleveland Indians, and I also would like to thank [former Indians farm directror] Ross Atkins and [senior director of scouting operations] John Mirabelli for their support. I enjoyed working with them."
Shapiro left the Indians after the 2015 season to serve as the president of the Blue Jays and brought Atkins to Toronto to work as his general manager.
Jordan Bastian is a reporter for MLB.com. Read his blog, Major League Bastian, follow him on Twitter @MLBastian and listen to his podcast. This story was not subject to the approval of Major League Baseball or its clubs.