The show originally debuted at East L.A. Community Television (formerly Buenavision Cable) in November 2000, before relocating to KCAT in March 2004, whose studio was located on the campus of Glen A. Wilson High School.

Throughout its run, Thee Mr. Duran Show has had in-studio guests such as comedian George Lopez, Los Angeles mayor Antonio Villaraigosa, actor Danny Trejo, professional boxer Mia St. John, KTTV journalist Tony Valdez, Operation Repo host Luis 'Lou' Pizarro, and radio personalities Art Laboe and Huggie Boy.

Some of the show's notable musical guests have included Lonnie Jordan of War, Brenton Wood, Thee Midniters, Tierra, Charles Wright & the Watts 103rd Street Rhythm Band, Redbone, American Idol Season 8 finalist Allison Iraheta, Klymaxx featuring guitarist Cheryl Cooley, and Cannibal and the Headhunters.

The show has also filmed interviews on location with actors Ana Ortiz, Mark Indelicato, Constance Marie, musicians Lalo Guerrero, Freddy Fender, Los Lobos, Malo, Ozomatli, El Chicano, Joe Bataan, Debbie Deb, Sheila E and athletes Oscar De La Hoya and Fernando Vargas.

Thee Mr. Duran Show has received a number of notable achievements, including being a finalist for the 2006 Western Video Excellence Awards in the Entertainment/Non-Pro category.