In 2000, Donahoe took on a job at ESPN.com for the following year.
Before the 2001 season, Donahoe was selected to replace John Butler as general manager of the Buffalo Bills, as well as take over the position of team president from a retiring Ralph Wilson. Wilson, while still maintaining ownership of the team, wanted to step aside from the day-to-day operations of the franchise, and chose Donahoe to take his place.
After the 2005 season, Donahoe was fired. The team had been 31–48 during his tenure with the team from 2001 to 2005, and he drafted only three players who would go on to make the Pro Bowl with the team.
Ralph Wilson re-assumed the role of president, and the general manager position was filled by former Bills head coach Marv Levy.