Since 2006, he has been principal owner and managing general partner of the Cincinnati Reds, leading a group that purchased a majority share of the Major League Baseball (MLB) franchise from previous CEO Carl Lindner, Jr. Castellini is the chairman of Castellini Co., a fruit and vegetable wholesaler.

In January 2006, Castellini was the head of a group who purchased the Cincinnati Reds baseball team.

[1] One of Castellini's first moves as CEO was replacing General Manager Dan O'Brien with Wayne Krivsky in February 2006.

Under Castellini's ownership in 2010, the Cincinnati Reds won their first National League Central division championship since the 1995 season.

Following the end of the 2022 MLB lockout, the Reds went on an apparent fire sale, leading to several fan protests over Castellini's ownership of the team and asking him to sell.