McInnes cofounded Vice in 1994 with Shane Smith and Suroosh Alvi.His role as an editor at Vice led to him being referred to as "the Godfather of hipsterdom" and one of the "primary architects of hipsterdom". He occasionally contributed articles to Vice, including The VICE Guide to Happiness and The VICE Guide to Picking Up Chicks, and coauthored two Vice books: The Vice Guide to Sex and Drugs and Rock and Roll, and Vice Dos and Don'ts: 10 Years of VICE Magazine's Street Fashion Critiques. He left Vice in 2007 due to "creative differences." In a 2013 interview with The New Yorker, McInnes claimed his split with Vice was about the increasing influence of corporate advertising on Vice's content, stating that "Marketing and editorial being enemies had been the business plan."

McInnes later created the website StreetCarnage.com. He also cofounded an advertising agency called Rooster where he serves as creative director. He writes for the web magazine Taki's Magazine,[19] and TruthRevolt and once wrote for Death and Taxes,[21] The Federalist, and VDARE.

In 2009, McInnes convinced a journalist at The Village Voice that he had been knocked out after losing a challenge to an MMA fighter. The footage was actually an outtake from a failed TV pilot. In 2010, McInnes convinced a journalist at Gawker that he had eaten a bowl of urinesoaked corn flakes after not winning their “Hipster of the Decade” competition. The footage was actually an outtake from a collection of comedy sketches called Gavin McInnes Is a Fucking Asshole.

An occasional standup comedian, McInnes directed a documentary on his standup comedy tour in 2013's The Brotherhood of the Traveling Rants. For the film, McInnes faked a serious car accident. That same year, he published a book of cartoons entitled How to Piss in Public.

In 2010, McInnes was approached by Adult Swim and asked to play the part of Mick an anthropomorphic Scottish soccer ball in the shortlived Aqua Teen Hunger Force spinoff Soul Quest Overdrive.[30] After losing a 2010 pilot contest to Cheyenne Cinnamon and the Fantabulous Unicorn of Sugar Town Candy Fudge, six episodes of Soul Quest Overdrive were ordered, with four airing in Adult Swim's 4 AM DVR Theater block on May 25, 2011 before quickly being cancelled. McInnes jokingly blamed the show's cancellation on the other cast members (Kristen Schaal, David Cross, and H. Jon Benjamin) not being "as funny" as him.

In 2013, McInnes starred in the independent film How to Be a Man, which premiered at Sundance Next Weekend.[32] He has also played supporting roles in other films including 2010's Soul Quest Overdrive and 2015's Creative Control and One More Time.

McInnes was featured in Season 3 of the Canadian reality TV show Kenny vs Spenny, as a judge in the "Who is Cooler?" episode.

In October 2013, McInnes was interviewed by The Huffington Post on a panel about masculinity. He said that "people would be happier if women would stop pretending to be men", and that feminism "has made women less happy". He explained that "We’ve trivialized childbirth and being domestic so much that women are forced to pretend to be men. They’re feigning this toughness, they’re miserable." A heated argument ensued with University of Miami School of Law professor Mary Anne Franks.

In August 2014, McInnes was asked to take an indefinite leave of absence as chief creative officer of Rooster, following online publication at Thought Catalog of an essay about transphobia entitled "Transphobia is Perfectly Natural" that sparked a call to boycott the company. In response, Rooster issued a statement, saying in part: "We are extremely disappointed with his actions and have asked that he take a leave of absence while we determine the most appropriate course of action."[37] McInnes defended the article by saying "All I was saying was transsexuals have a huge suicide rate," and calling the reaction "fake hysteria."

In June 2015, Anthony Cumia announced that McInnes will be hosting a show on his network, therefore retiring the Free Speech podcast. The Gavin McInnes Show premiered on Compound Media on June 15 and airs Monday through Thursday at 10:30 A.M EST.

McInnes is a contributor to Canadian conservative portal The Rebel Media and a regular on Fox News' Red Eye, The Greg Gutfield Show, and The Sean Hannity Show.