The two stations share studios at Broadway and Battery Street, just north of San Francisco's Financial District; KPIX's transmitter is located atop Sutro Tower.

In addition to KPYX, KPIX shares its building with formerly co-owned radio stations KCBS, KFRC-FM, KITS, KLLC, KRBQ and KZDG, although they use a different address number for Battery Street (865 as opposed to 855).

KPIX signed on the air on December 22, 1948, the first television station in Northern California as well as the 49th in the United States.

Initially, channel 5's signal was transmitted from the top of the Mark Hopkins Hotel on Nob Hill.

[3] The station immediately joined CBS due to a deal KSFO's owners had worked out with the television network one year earlier.

When KSFO was still affiliated with CBS, it was originally slated to move to 740 AM, the frequency of San Jose's KQW.

After lengthy Federal Communications Commission (FCC) hearings, KSFO won the 740 frequency, but later decided to stay at 560 and concentrate its efforts on building a television station.

Under its first general manager, Phil Lasky, KPIX gained an early reputation for news coverage, being noted for originating national CBS coverage of the Japanese Peace Conference of 1951 (the event which "officially" brought an end to World War II, similar to the function that the Treaty of Versailles served for World War I), held in San Francisco (for which Lasky was commended by then-CBS News president Sig Mickelson), as well as local news coverage of the 1953 crash of an Australian airliner while on approach to San Francisco International Airport, and a powder explosion a few weeks afterward at an explosives plant in suburban Hercules.

KPIX originated the annual college football East-West Shrine Game for DuMont, and was the flagship station of the San Francisco Seals of the Pacific Coast League until 1954.

Westinghouse Electric Corporation bought KPIX in 1954 and ran it as part of the company's Group W broadcasting unit.

Ultimately, Westinghouse signed a long-term deal with CBS to convert the entire five-station Group W television unit to a group-wide CBS affiliation, making the San Francisco market one of the few major markets that were not affected by the affiliation switches.

[12][13] In late 1995, Westinghouse merged with CBS, making KPIX a CBS-owned station and bringing it into common ownership with KCBS radio.

Eye on the Bay ended its weekday broadcasts on September 7, 2012, and switched to a weekly program on Saturdays thereafter.

From 1956 to 1993, KPIX carried most San Francisco 49ers games locally as part of CBS' broadcast rights to the NFL, which covered the entire pre-merger league until 1970, and the National Football Conference from 1970 to 1993.

In 1994, CBS was outbid for television rights by Fox, and most Sunday 49ers games have been broadcast by KTVU (channel 2) since.

Beginning in 1998, the NFL on CBS returned to KPIX, originally with the American Football Conference Sunday package.

Beginning in 2014, the NFL can schedule Sunday day games on either CBS (KPIX) or Fox (KTVU) regardless of conference.

[19] KPIX also locally broadcasts some 49er games which are on pay television, including ESPN Monday Night Football or streaming services.

During the 1950s, KPIX produced a local children's program, Captain Fortune, on weekday afternoons and Saturday mornings.

In addition to a number of live segments with an in-studio children's audience, the program featured the animated television episodes of Crusader Rabbit.

Brother Buzz, a feature from the Latham Foundation (an Oakland-based organization dedicated to the concept of humane education), with marionettes created and operated by Ralph Chesse and company, were a weekly segment starting in 1952 (and later became its own separate, stand-alone program which ran for several more years on KPIX and KGO).

[21] Abenheim wrote the screenplay for a 1962 science fiction film, This Is Not a Test (also released as Atomic War Bride).

[23] From 1956 to 1959, Davenport, Iowa, native Dick Stewart (born 1927) hosted a weekday variety program at KPIX.

On January 28, 2008, KPIX became the third Bay Area television station to begin broadcasting its local newscasts in high definition (behind KGO-TV and KTVU); most field reports were initially still broadcast in 4:3 standard definition (albeit pillarboxed); KPIX started using HD cameras for its field reports in September 2010; however, not all of the station's news footage is shot in HD.

In September 2010, KPIX introduced new graphics for its newscasts, a standardized package that was also rolled out to CBS's other news-producing O&O stations; this included the addition of "The Enforcer" music package by Gari Media Group, the basic theme of which has been used on many CBS-owned stations since the mid-1970s, when it was introduced by WBBM-TV.

On January 8, 2012, KPIX began producing a Sunday morning newscast for sister station KBCW.

[28] On September 27, 2021, KPIX launched a half-hour 3 p.m. newscast, followed by the live East Coast feed of the CBS Evening News.