The station, initially operating an ABC affiliate, first signed on the air on September 16, 1961, at 2 p.m. Eastern time with the dedication program entitled Kickoff 32.

[2] It originally operated from studio facilities located on Park Drive in the suburb of Shively, and was owned by Kentuckiana Television, a group of local investors headed by aluminum magnate Archibald Cochran.

These factors caused the first attempt at a full-time ABC affiliate in the area, WKLO-TV, UHF channel 21, to shut down after only six months on the air.

But, a growing Louisville market and a stronger-performing ABC, with new programming like American Football League games and more popular prime time shows (e.g. Desilu's The Untouchables), convinced Cochran to take a chance on starting the station.

[2]: 289 In the spring of 1983, Gannett sold WLKY and WPTA in Fort Wayne, Indiana (the two smallest stations by market size in Gannett's television station portfolio at the time), to Pulitzer Publishing, after it purchased WLVI-TV in Boston (now owned by Sunbeam Television) from Field Communications and WTCN-TV (now KARE) in Minneapolis–Saint Paul from Metromedia.

The switch to CBS provided a major windfall for WLKY that winter, as it became Louisville's home for the NCAA men's basketball tournament.

On July 9, 2012, WLKY's parent company Hearst Television became involved in a carriage dispute with Time Warner Cable after that company's purchase of the market's major cable provider Insight Communications, leading to WLKY's removal from Time Warner Cable and its temporarily replacement by Rochester, New York, CBS affiliate WROC-TV (owned by Nexstar Broadcasting Group);[5][6] Time Warner chose to replace the station with WROC-TV as it did not have any rights to carry any other CBS affiliate within the region.

It is also considered a rarity for a Hearst-owned station because WLKY is one of only fifteen stations owned by Hearst (alongside NBC affiliates KCRA-TV in Sacramento, WXII-TV in Winston-Salem, WESH in Orlando, WVTM-TV in Birmingham, WDSU in New Orleans, WBBH-TV in Fort Myers and WGAL in Lancaster, Pennsylvania, and ABC affiliates WISN-TV in Milwaukee, KMBC-TV in Kansas City, KOAT-TV in Albuquerque, WMUR-TV in Manchester, New Hampshire, WMTW in Portland, Maine, WPBF in West Palm Beach and WTAE-TV in Pittsburgh) that carry a full midday newscast, whereas most Hearst stations either do not carry one at all or carry a half-hour midday newscast and fill the remainder of the hour with either syndicated or paid programming.

For most of its tenure as an ABC affiliate, WLKY was one of that network's weaker stations in terms of local viewership, usually ranking third in the Nielsen ratings.

In the recent February 2013 sweeps period, WLKY and Fox affiliate WDRB (channel 41) began distancing themselves from WHAS and WAVE in total-day ratings, largely due to their higher-rated syndicated and local programming lead-ins to their newscasts.

In February 2012, WLKY debuted a two-hour extension of its weekday morning newscast, airing from 7 to 9 a.m., on its MeTV affiliated second digital subchannel.

The station's signal is multiplexed: On September 1, 2011, WLKY began carrying the Weigel Broadcasting-owned classic television network MeTV on digital subchannel 32.2, which is also available on Spectrum 188.

As part of the SAFER Act,[16] WLKY kept its analog signal on the air until July 12 to inform viewers of the digital television transition through a loop of public service announcements from the National Association of Broadcasters.

[20] Both WLKY and WTVF (as well as their associated digital subchannels) remain available in Glasgow (Barren County) on the cable system of the South Central Rural Telephone Cooperative.

In the Evansville, Indiana, market, Crystal Broadband Networks carries WLKY on CBN channel 2 on its lineup for the system's customers in Hancock County, Kentucky, including the towns of Hawesville and Lewisport.