Von began a professional career in entertainment at age nineteen when he starred in MTV’s Road Rules: Maximum Velocity Tour in 2000. He was recruited to the show while studying at Louisiana State University.

Following his season of Road Rules, Von was on four seasons and nearly seventy episodes of MTV’s reality game show The Challenge, formerly known as Real World/Road Rules Challenge. The show was a spin off of MTV’s The Real World and Road Rules. He was part of the cast of the seasons Battle of the Seasons (2002), The Gauntlet (2003–2004), Battle of the Sexes II (2004–2005), and Fresh Meat (2006). Von was runner-up in 2002 and won the following two seasons. Concurrently to the airing of Real World/Road Rules Challenge in 2006, Von competed on Last Comic Standing.

Von achieved one of his first major comedic accomplishments a few years later in 2006 when he won the title of Fan Favorite on the online competition aligned with the fourth season of Last Comic Standing. Around this time, Von also began touring his set nationally. He also took part in five international tours for the USO which included performing at Guantanamo Bay.

He returned to reality TV in Spring 2008, when Von was a panelist on the 2008 short-lived ABC Family reality competition show America’s Prom Queen. In the summer of 2008, Von was one of the members of the Comedy Central sketch/competition show Reality Bites Back. Von won the show, beating out fellow comedians Amy Schumer, Bert Kreischer, and Tiffany Haddish, among others.

In 2009, Von popularized “crank texting” (sending a text message to random phone numbers to incite conversations), and began his “crank texting” blog, which was picked up as a column by CollegeHumor a year later.

Von grew up in Covington, Louisiana with his older brother and two younger sisters, all of whom currently reside in Baton Rouge, Louisiana. Von was legally emancipated at age fourteen. He graduated from Mandeville High School in Mandeville, Louisiana. He attended Louisiana State University for a time, as well as Loyola University New Orleans, University of Arizona, College of Charleston, and Santa Monica College. Von received his undergraduate degree in 2011 from the University of New Orleans.

Beginning in 2011, Von took over as a host of the popular Yahoo online TV recap show Primetime in No Time. Von hosted the TBS hidden camera show Deal With It, executive produced by Howie Mandel, for its run of three seasons from 2013 to 2014.

In April 2011, Von began his first podcast, The Comedy Sideshow. Taped at the Improv Comedy Club in Hollywood, Von would interview comedians and other entertainers. The show had twenty-three episodes, the last of which premiered in November of that year.

On June 1, 2012, Von was the featured comedian in an episode of Comedy Central’s The Half Hour, now known as Comedy Central Stand-Up Presents. He also promoted his comedy on The Arsenio Hall Show, Hello Ross, Chelsea Lately, Watch What Happens Live, @midnight, and This Is Not Happening, among other television shows. In 2016, Netflix released Von’s debut hour-long comedy special No Offense. The show was taped at the Civic Theatre in New Orleans, Louisiana. In Summer 2019, Von embarked on a three-month national tour called The Dark Arts Tour.

In 2015, Von started a weekly podcast with Matthew Cole Weiss called Allegedly with Theo Von & Matthew Cole Weiss. Two totally opposite friends – comedian Theo Von and filmmaker/journalist Matt Cole Weiss – compete to see who has better “alleged” tales of celebrities, hilarity, trauma, dating, success and failure from their years living in Hollywood. The podcast lasted three years and had a total of 123 episodes.

Von began a new podcast in December 2016, This Past Weekend. The show is a long-form video podcast which features Von storytelling, answering fan voicemails, as well as thoughtful guest interviews. Von released his two-hundredth episode in May 2019.

In Spring 2018, Von’s three-episode scripted comedy show Man Up was released on Comedy Central. In August 2019, Von announced that he had been cast in the big-budget film Ghost Draft and had been recruited to the project by its star Chris Pratt. A few weeks later, Von announced on his podcast that he had dropped out of the movie due to the time commitment.

In December 2018, Theo Von and comedian Brendan Schaub started a new podcast called The King and The Sting. At the podcast’s release, The King and The Sting debuted #1 on the iTunes Podcast charts in the United States and also reached the top charts in the United Kingdom, Canada, Spain and Australia.

As of 2020, Von hosts two podcasts, This Past Weekend and The King and The Sting. Von has been a recurring guest on many comedian’s podcast including The Joe Rogan Experience, Joey Diaz’s The Church of What’s Happening Now, The Fighter and the Kid, and Bobby Lee’s TigerBelly, among others.