Throughout his career, he promoted a wide variety of products, including OxiClean, Orange Glo, Kaboom, Zorbeez, and Mighty Mendit.

Mays and his business partner, Anthony Sullivan, were also featured on PitchMen, a Discovery Channel television series that documented their work.

His distinctive beard, attire, loud voice, and impassioned sales pitches made him a recognized television presence in the United States and Canada.

[9] At a Pittsburgh, Pennsylvania, home show in 1993, Mays struck up a friendship with rival salesman Max Appel, founder of Orange Glo International, a Denver-based manufacturer of cleaning products.

For example, The Washington Post staff writer Frank Ahrens called him and other similar television salesmen "a full-volume pitchman, amped up like a candidate for a tranquilizer-gun takedown".

[15] On April 15, 2009, the Discovery Channel began airing PitchMen, a documentary series that featured Mays and Anthony Sullivan in their jobs in direct-response marketing.

[21] He had a son with Dolores named Billy Mays III (born August 12, 1986) who worked as a production assistant alongside his father on the PitchMen television show.

Initially, there was incorrect speculation that he died from a head injury he experienced on a flight he had taken earlier in the day, in which the plane sustained a rough landing after blowing its tires.

[31] According to subsequent news reports,[32] the toxicology tests also showed levels of painkillers hydrocodone, oxycodone, and tramadol, as well as anti-anxiety drugs alprazolam and diazepam.

[35][36] His catchphrase and infomercials made Billy Mays a notable icon in popular culture, with many shows, YouTube videos, and films lampooning him.

Mays' son, Billy III, a self-proclaimed South Park fan, said he loved "Dead Celebrities", and found its portrayal of his father to be both tasteful and respectful.

[37] He was portrayed by comedian Colin J. Sweeney in the season 1 episode of Epic Rap Battles of History, "Billy Mays vs. Ben Franklin".

In the middle of the battle, Mays dies and has his second verse covered by fellow infomercial pitchman, Vince Offer, portrayed by Peter Shukoff.