He was nominated for a Writers Guild of America Award for Best Dramatic Series at the February 2009 ceremony for his work on the fourth season.

[3] Wired describes Vaughan's comics work as "quirky, acclaimed stories that don't pander and still pound pulses".

His creator-owned comics work is also characterized by "finite, meticulous, years-long story arcs", on which Vaughan comments, "That's storytelling, with a beginning, a middle, and an end.

[9] Vaughan also cites Joss Whedon as the reason he wanted to become a writer,[10] a decision he made while attending St. Ignatius High School, from which he graduated in 1994.

[15] Vaughan wrote his own screenplay for the project,[4] though it was reported in March 2012 that Matthew Federman and Stephen Scaia were in final negotiations to write their own version.

[16] In 2006, Vaughan published the graphic novel Pride of Baghdad, which centers on a group of lions who escape from an Iraqi zoo after the start of the Iraq War.

[18] From 2004 to 2010 Vaughan wrote another creator-owned series, Ex Machina, a political thriller that depicts the life of Mitchell Hundred, a former superhero known as the Great Machine who, in the wake of his heroism during the September 11, 2001 attacks, is elected Mayor of New York City.

[8] That episode was praised by Wired writer Erik Malinowski, who stated that the themes that Vaughan carried over to Lost from his comics work, including intricately crafted storylines typified by pathos and hope, as well as pop culture references, redeemed that series' third season.

He was also a co-producer on Lost: Missing Pieces, a spinoff Internet short film series produced during the hiatus between the show's third and fourth seasons.

[27] The series has received positive reviews[28] from MTV,[29] Ain't it Cool News,[30] Comic Book Resources,[31] IGN,[32] Publishers Weekly[33] and Time magazine.

[37] In March 2013, Vaughan published the first issue of The Private Eye with artist Marcos Martín on Panel Syndicate, a pay-what-you-want host for their creative efforts.

[42] Hamburger has also appeared in an illustration of Vaughan and Fiona Staples that was included in a 2013 Time magazine story on Saga.