The station first signed on the air on December 31, 1953 as WFBC-TV; it was the fifth television station to sign on in South Carolina, and transmitted its signal from a tower located on Paris Mountain. The station was owned by the Peace family and their News-Piedmont Publishing Company alongside local newspapers The Greenville News and The Greenville Piedmont, and was a sister station to WFBC radio (1330 AM, now WYRD, and 93.7 FM).
In 1961, the News-Piedmont Publishing Company purchased WBIR-AM-FM-TV in Knoxville, Tennessee from the former Taft Broadcasting Company. News-Piedmont merged with Southern Broadcasting to form Multimedia, Inc., with WFBC-AM-FM-TV as the company's flagship stations.
WFBC-TV began using the "Your Friend 4" slogan in 1979, which would form the basis of its next callsign in 1983.
WFBC-TV changed its callsign to the current WYFF-TV on March 3, 1983 after Multimedia traded to the Pulitzer Publishing Company in exchange for KSDK (VHF channel 5) in St. Louis; it retained the "arrow 4" logo it had been using since 1973.