It initially aired programming from all of the national networks, though it gradually lost them from 1953 onward as new stations signed on in the Phoenix area once the freeze ended.

L. Wheelock, W. L. Pickens, H. H. Coffield, and John B. Mills—filed an application with the Federal Communications Commission for a construction permit to build a new television station on channel 5, which was granted on June 2.

The venture united Mills, the owner of downtown Phoenix's Westward Ho hotel, with three Texas oilmen.

[5] By summer, construction had begun on a building adjacent to the Westward Ho, at 631 N. First Avenue, to house offices and studios for the station, which initially had the call letters KTLX.

[7] Arizona's first television station began broadcasting on December 4, 1949; network coaxial cables had not reached Phoenix, so all programs were either on film or live.

[13] The end of the FCC freeze in 1952 started the process that would bring to the Phoenix area three new television services within less than two years.

[16] KOOL-TV then relinquished ABC to KTVK, which went on the air in February 1955, and became the new CBS affiliate on June 15 of that year—starting nearly four decades of independent television at channel 5.

[19][20] From 1966 to 1967, the station was the subject of a 13-month NABET strike, then the longest in state history, which ended when the workers disavowed the union by a vote of 49 to 3.

[21] In 1970, ground was broken on a new, 42,000-square-foot (3,900 m2) studio facility on Black Canyon Highway south of Indian School Road, which the station occupied in 1971.

[23] While KPHO-TV gained its first independent competition in 1967, with the arrival of KPAZ-TV on channel 21, the new outlet focused more on specialty and Spanish-language programs.

It was little competition for channel 5, which was found by an American Research Bureau survey in 1975 to be the number-one independent station in the country in terms of viewing share.

By this time, KPHO-TV was the third highest-rated station in Phoenix in total-day ratings, ahead of KTVK, long an underperforming ABC affiliate.

[26] By 1991, with KNXV and 1985 startup KUTP cutting into channel 5's ratings alongside the rise of cable TV and the VCR, Barbara Holsopple, media writer for the Phoenix Gazette, declared that KPHO was "fighting for its life".

[32]) CBS officially returned to KPHO on September 10, 1994,[33] three days after New World's purchase of KSAZ-TV—which became an independent before affiliating with Fox three months later—was finalized.

A $1 million promotion blitz was undertaken by Meredith and CBS, along with a planned doubling of the station's local news output.

As FCC rules restrict one company from owning more than two television stations in the same market, Gannett announced that it would spin off KTVK and KASW to Sander Media, LLC, a company operated by former Belo executive Jack Sander, with their operations to remain largely separate from KPNX and The Republic.

The Department of Justice required the outright sale of one of the two St. Louis stations in lieu of a transfer to Sander, noting a combination of the two would put Gannett in a dominant position in the local advertising market.

On August 7, Meredith announced plans to merge the two stations' operations at KTVK's studio in the Central Avenue Corridor, citing its significantly larger size in comparison to KPHO's facilities.

[40] On May 3, 2021, Gray Television announced its intent to purchase the Meredith Local Media division, including KPHO and KTVK, for $2.7 billion.

[44] This program shifted to 9:30 p.m. in 1975, where it remained for more than 15 years, with the station producing an hour of news a day: a midday show at 11:30 a.m. and a 9:30 p.m. newscast.

It often out-rated KTVK and by 1985, in the words of The Arizona Republic television columnist Bud Wilkinson, had managed to "stake a firm claim as the third-rated news department in town".

[47] KPHO reassuming the CBS affiliation required massive changes in the newsroom, including an expanded staff, in order to begin production of a variety of newscasts that channel 5 did not offer.

[70][71] As part of the SAFER Act,[72] KPHO kept its analog signal on the air until June 26 to inform viewers of the digital television transition through a loop of public service announcements from the National Association of Broadcasters.