Penn Jillette is a raconteur; Teller (generally) does not speak while performing, although his voice can be heard as the narrator throughout their performance. They specialize in gory tricks, exposures of fakers and of some magic tricks, and clever pranks, and have become associated with Las Vegas, atheism, scientific skepticism, and libertarianism. They call themselves "a couple of eccentric guys who have learned how to do a few cool things.

The duo met in 1975 and from the late 1970s through 1981, Penn & Teller were part of a three-man act called "Asparagus Valley Cultural Society" which played in San Francisco at the Phoenix Theater. This act was sillier and less "edgy" than today's Penn & Teller act. The third member of the AVCS, Weir Chirsamer, helped to develop some bits that have continued on, most notably Teller's "Shadow-Flower" trick.

By 1985, Penn & Teller were receiving rave reviews for their Off Broadway show and Emmy award-winning PBS special, Penn & Teller Go Public. In 1987, they began the first of two successful Broadway runs. Through the late 1980s and early 1990s, the pair made numerous television appearances on Late Night with David Letterman and Saturday Night Live, as well as The Tonight Show with Jay Leno, Late Night with Conan O'Brien, The Today Show, and many others.

Penn & Teller had national tours throughout the 1990s, gaining critical praise. They have also made television guest appearances on Babylon 5, The Drew Carey Show, Hollywood Squares, The Bernie Mac Show, Fear Factor, The West Wing, Home Improvement, Sabrina the Teenage Witch, and The Simpsons. They also appeared as scam artists in the music video for "It's Tricky" by Run-DMC in 1987.

The pair have written several books about magic, including Penn & Teller's Cruel Tricks For Dear Friends, Penn & Teller's How to Play with Your Food, and Penn & Teller's How to Play in Traffic.

Since 2001, Penn & Teller have performed six nights a week in Las Vegas at the Rio All Suite Hotel and Casino.

Penn Jillette began a weekday one-hour talk show on Infinity Broadcasting's Free FM radio network in January 2006 with co-host Michael Goudeau.