WGN Radio president Jimmy De Castro said Wednesday "today is a tough day," because of the station's 90-year relationship with the team.
"It's not that we don't love the Cubs," de Castro said. "It's that it just doesn't make business sense on an AM radio station given today's new media opportunities and ways for advertisers to buy the Cubs."
WGN Radio had exercised an option to re-open its contract.
WBBM-AM 780 also carries the Chicago Bears' NFL games.
Cubs radio broadcasters Pat Hughes and Ron Coomer were expected to stay.
Carrie Muskat is a reporter for MLB.com. She writes a blog, Muskat Ramblings, and you can follow her on Twitter @CarrieMuskat. This story was not subject to the approval of Major League Baseball or its clubs.