WPXO originally began as an independent station on channel 23 with the call letters W23BA. In 1996, the station was sold to Paxson Communications, which made it a translator for its station in Bridgeport, Connecticut, WHAI-TV. After Paxson acquired WPXN-TV to serve as its New York outlet, the company sold off the Bridgeport station (which has since become WZME) and made W23BA a translator of WPXN. The following year, due to potential future interference from WHSI-TV (now WFTY-DT), who was assigned channel 23 for its digital signal, it moved to channel 34.

On September 11, 2001, the transmitter facilities of WPXN, as well as six other New York City television stations and several radio stations, were destroyed when two hijacked airplanes crashed into and destroyed the World Trade Center towers. The next day, the Federal Communications Commission (FCC) authorized W23BA to temporarily move its signal to channel 31, boost its power to 240 kW, and change its call letters to W31CK to replace WPXN's signal. When WPXN-TV returned to the air with a new transmitter on the Empire State Building in 2002, W31CK's signal moved back to channel 34 and was assigned W34CP as its new call letters. A year later, the station became WPXO-LP.

In August 2007, WPXO was sold to Caribevision Station Group, LLC. It re-launched on September 11, 2007 as an affiliate of new network CaribeVision. The station's programming consisted mainly of Argentinian and Brazilian telenovelas (Yago, pasión morena, Mi primer amor -originally known in Argentina as Romeo y Julieta-, etc.), talk shows (Margarita, te voy a contar), sitcoms (Here's Lucy, Poné a Francella), infomercials during the mornings and public domain cartoons on weekends.

During the week of May 4, 2009, WPXO-LP turned off its analog signal on channel 34 and began test broadcasts on digital channel 34, and as of late May, WPXO has been transmitting its programming full-time on digital channel 34.