[3] In January 1995, WISC-TV began maintaining a secondary affiliation with UPN, carrying tape-delayed overnight airings of the network's prime time programming following CBS's late-night lineup; this arrangement ended in July 1999, when Media Properties Inc. signed on Janesville-licensed WHPN-TV (channel 57, now Ion Television affiliate WIFS) as Madison's first full-time UPN outlet.

In 1998, WISC-TV partnered with Internet Broadcasting Systems to become the first TV station in the region, and one of the first in the country, to have a dedicated news website, "Channel 3000".

The channel maintained a format modeled after general entertainment independent stations, running a mix of syndicated sitcoms, drama series, talk shows and game shows; children's programming (including some off-network cartoons); a limited schedule of local news and community affairs programs; regional sporting events (including Milwaukee Bucks basketball games carried by the team's then-originating broadcast affiliate, WVTV); and an early-morning simulcast of Bloomberg Information Television (renamed Bloomberg Television in 1997).

On August 26, 2002, WISC-DT2—which, accordingly, adopted "UPN14" as its branding—became the market's UPN affiliate as part of an affiliation swap with WHPN—which concurrently changed its calls to WBUW—that was tied to the April 2 sale of the latter to ACME Communications (a station group founded by WB co-founder and former network president Jamie Kellner),[5] thus allowing area viewers who neither had a cable or satellite subscription nor an HDTV set (and therefore, lacked access to TVW's broadcast and cable feeds) to watch WB network programs for the first time.

On March 8, 2006, Morgan Murphy Media confirmed that WISC-DT2 would become the Madison-area charter affiliate of MyNetworkTV, developed as a joint venture between then-News Corporation subsidiaries Fox Television Stations and 20th Television (the former is now owned by Fox Corporation; the latter has since been integrated into Disney Media Distribution as a result of Disney's 2019 acquisition of most of 21st Century Fox's assets) and announced on February 22 to primarily serve as a network option for UPN and WB stations that were not chosen to affiliate with The CW (co-founded by their then-respective parents, CBS Corporation and Time Warner, to replace both networks).

On July 1, 2009, WISC-DT2 reverted to the former "TVW" brand, accompanied by new blue/white/black circular logo; the rebranding was meant to emphasize a connection to Madison and Wisconsin in the channel's programming.

[9] In February 2019, TVW acquired the rights to selected syndicated programs and most of the locally produced programming—including the Saturday night horror movie showcase Bordello of Horror and Talk Wisconsin (previously titled Talk of the Town before the show relocated)—that had been displaced from WIFS after it converted into an Ion Plus affiliate with little advanced notice to its viewers on February 1.

WISC was home to ESPN Plus broadcasts of Wisconsin Badger sports before the syndicator's relationship with the Big Ten Conference ended in 2007.

These games originated from Weigel's Milwaukee CBS affiliate WDJT-TV and independent station WMLW-TV and utilize Bally Sports commentators and production personnel.

[15] On October 26, 2008, WISC-TV began producing all its newscasts in total high-definition video, becoming the first commercial TV station in Wisconsin to do so.

[17] The station's signal is multiplexed: WISC-TV ended regular programming on its analog signal, over VHF channel 3, at 12:30 p.m. on February 17, 2009, the original target date on which full-power television stations in the United States were to transition from analog to digital broadcasts under federal mandate (which was later pushed back to June 12, 2009).