KOSU began broadcasting in 1955 and was a charter member of NPR. Shortly after joining NPR, the station built a new tower roughly halfway between Oklahoma City and Tulsa, so that each city got grade B coverage and most of the suburban areas got city-grade coverage.
In September 2004, KOSU moved to a new 1,100-foot tower near Guthrie that gave it primary coverage of Oklahoma City. KOSU also added improved service to northeastern Oklahoma with the purchase of commercial station KGND in Ketchum in September 2004 by Public Radio Capital, which entered an LMA with Oklahoma State University to simulcast the KOSU signal. On the same day KOSU moved to its new tower, KGND changed its calls to KOSN.
In March 2006, KOSU added two new translators in the Tulsa area, at 101.9 FM in Okmulgee (owned by PRC) and 107.3 FM in Bixby (owned directly by OSU). In 2011, KOSU added a new station on KOSR 88.3 FM in Stillwater.
On August 20, 2012, KOSU unveiled a new tag line, "Uniquely Oklahoma", and implemented changes in their daily schedule with new news/talk and music programs. At the core of the changes was a content partnership with "The Spy", which can be heard on weeknights and sporadically on the weekends on KOSU.
In February 2013, Oklahoma State University received a $150-thousand grant from the Ethics and Excellence in Journalism Foundation in support of a new broadcast facility for KOSU. In September 2013, KOSU's Oklahoma City studios opened in the Hart Building in the historic Film Exchange District (Film Row). The new studios include a digital newsroom and a public performance studio that can accommodate up to 50 guests for concerts and community conversations. KOSU now originates live broadcasts from the downtown Oklahoma City studios as well as its original studios on the OSU campus.
In June 2014, KOSU announced that it would be joining the Clinton Global Initiative Project to Preserve American Indian Languages. "KOSU is committing its facilities and expertise during the next year to produce 250 book narrations in five indigenous languages."