In September 2000,[6] he started work on his self-published black and white comic series Chiaroscuro with which he was awarded in 2001 a Xeric Grant.

[3] In late 2005, he had completed his first storyline as the graphic novel Chiaroscuro: Patchwork Book 1 (collecting issues #1-10), and started sending out a 100-copy POD run[3] to publishers.

In 2007, this first volume of Chiaroscuro received an excellent review by independent comics legend Dave Sim (creator of Cerebus) written on his Blog & Mail.

In January 2009, Troy Little released Angora Napkin, a standalone graphic novel from IDW Publishing which was nominated for an Eisner Award.

During the Fear and Loathing in Las Vegas book tour Little met Kevin Eastman, co-creator of the Teenage Mutant Ninja Turtles.

In 2017 Eastman tapped Little to help develop his Drawing Blood / Radically Rearranged Ronin Ragdolls series which was successfully Kickstarted in published in 2018.

In 2018, Little teamed up with writers Jim Zub and Patrick Rothfuss for the limited series Rick and Morty vs. Dungeons & Dragons #1-4, published by IDW.