WOSU-FM signed on for the first time on December 13, 1949. It initially simulcast its AM sister from sign-on until 6:45 pm, then broadcast separate programming until signing off at 7:30 pm. In 1950, the broadcast day was extended to 9:15 pm. It began 24-hour operation in 1960, and began airing a fully separate schedule on October 1, 1968. The station broadcast an all-classical format from 1980 until 2008.
It was the first station in Columbus to broadcast using HD Radio, beginning on April 5, 2004, at 3:30 p.m. It was also the first station in the United States to begin full-time multicast broadcasting when its HD-2 channel debuted on October 15, 2004.
From January 14, 2008, WOSU-FM switched to a mixed news/classical format, introducing NPR news magazines during morning and evening drive-times along with several popular NPR weekend programs such as Weekend Edition, Car Talk, and Wait Wait... Don't Tell Me!, plus This American Life from Public Radio International. Many of these programs were simulcast with its AM sister station WOSU-AM. The station now features a 24-hour-a-day classical music service on its HD-2 HD Radio stream as well as on its web site.
In Fall 2010, Ohio State University purchased commercial station WWCD; that station was soon given new call letters - WOSA - and switched to a full-time classical music station. WOSU-FM switched to a full-time NPR news/talk format, simulcasting with WOSU-AM, though the FM station is now branded as the main station. WOSU also converted four of its satellite stations, WOSB in Marion, WOSE in Coshocton, WOSP in Portsmouth and WOSV in Mansfield, to repeaters of WOSA. In particular, WOSB and WOSV serve areas north of Columbus that are not served well by the new 101.1 frequency.