[2] His written work includes All-New Hawkeye, Extraordinary X-Men, Moon Knight and Old Man Logan for Marvel; Superboy, Animal Man, Justice League Dark, and Green Arrow for DC; Black Hammer and Mazebook for Dark Horse; Descender and Gideon Falls for Image Comics; and Bloodshot Reborn for Valiant.

[5] Lemire has also collaborated with musicians such as Eddie Vedder on his Matter of Time animated video and Gord Downie on Secret Path, a multimedia storytelling project.

[7] After self-publishing the Xeric Award-winning comic book Lost Dogs in 2005 via his Ashtray Press imprint, Lemire found a home at Top Shelf Productions.

In 2006 Lemire's work was included in an international symposium gathering artists, scholars, curators, publishers, librarians, critics, and writers at the Banff Centre.

In June 2011 it was announced that visual effects artist John Dykstra will direct an adaptation of Essex County entitled Super Zero.

[9][10][11] In December 2015, it was announced that First Generation Films had optioned the rights to Essex County to develop the graphic novel as a television series from Canada's CBC.

In 2009, DC Comics' Vertigo imprint published Lemire's The Nobody, a two-colour tale of identity, fear and paranoia in a small community.

[27][28] He continued to write Animal Man into 2012, including teaming up with Swamp Thing writer Scott Snyder for a crossover between the two books called "Rotworld.

[35] Lemire wrote Teen Titans: Earth One, an original graphic novel with art by Terry and Rachel Dodson published by DC Comics in November 2014.

[50] Spinning out of The Valiant, Lemire began writing the ongoing series Bloodshot Reborn alongside artist Mico Suayan, with the first issue being released in April 2015.

[51] The series features Bloodshot, a character Lemire approached by distilling the issues he had him and twisting the prototypical action hero into a more emotionally-driven story.

[54] In March 2015, Lemire launched Descender, a creator-owned science fiction series with art by Dustin Nguyen, from Image Comics.

[62] In July 2014, Dark Horse Comics announced a new creator-owned superhero series written by Lemire with art by Dean Ormston, titled Black Hammer, set to be released in March 2015.

[69] Plutona, a five-issue limited series from Image Comics co-written with artist Emi Lenox, was released in September 2015 to critical acclaim.

[70][71] Announced at Image Expo 2015, the series follows a group of kids who find the body of a dead superhero in the woods, and features colors by Jordie Bellaire.

[74] The graphic novel, which Lemire wrote, illustrated, and painted, follows a former hockey player's slide into depression as interrupted by the arrival of his sister, and was scheduled to be published in October 2016.

[76] AD: After Death, a graphic novel written by Scott Snyder and illustrated by Lemire, was announced at Image Expo 2015 for release on November of that same year.

Written by Jeff Lemire with art by Gabriel Hernández Walta, Sentient was nominated for the Eisner Award for Best Limited Series in 2020.

In early September 2021, Lemire announced his Tales from the Farm email newsletter would be moving to Substack, where he would be serializing a new story, Fishflies.

"[95] In November 2021, Lemire announced the project as The Bone Orchard Mythos, a "shared horror universe of interconnected stories taking place across multiple books and in different formats" from him and Sorrentino at Image Comics.

[96] In May 2020, Jeff Lemire and Matt Kindt announced the opening of a Kickstarter crowdfunding campaign for a graphic novel entitled Cosmic Detective, for which they will be writers with David Rubín on board as artist.

[99] Originally announced under the codenames "Project Jackknife" and "Project Headlights," Phantom Road is a collaboration with artist and co-creator Gabriel Hernández Walta, colorist Jordie Bellaire, and letterer Steve Wands, which Lemire calls "ambitious" and a "longer story" with at least three different story arcs,[93] currently planned for a November 2022 release.

[101] He was a 2008 recipient of a Young Adult Library Services Association Alex Award for Essex County Volume 1: Tales from the Farm.

[104] 2013 saw Lemire win another Joe Shuster Award for Outstanding Cartoonist (recognizing his work on Sweet Tooth and The Underwater Welder).

[67] Lemire has also been nominated for an Ignatz, a Harvey, and multiple other Eisner Awards (most recently for Barbalien: Red Planet by Dark Horse).