The writer will revive the former Top Cow Productions imprint at Image Comics, reports Deadline.
The move comes as part of the launch of the multi-platform Studio JMS, which will collect all of Straczynski's comic books, digital, television series, feature films and video games output under one roof.
Joe's Comics - which ran from 2000 to 2004 - was formerly the home of titles including Midnight Nation and Rising Stars.
It will return with four new titles - Falling Angel, Ten Grand, Guardians and Sidekick.
"The centre of the storm is what comes out of my keyboard," said Straczynski. "It's all about creating IP.
"For 20 years, I've had the remarkable good fortune to work successfully as a writer and producer in a wide variety of fields, from television to comics and movies. I've always dreamed of creating a mini-studio where I can put all of that work under one roof, telling stories that I want to tell and which can be spun up between various platforms: comics that can become TV shows, TV shows that can become movies and movies that can become comics.
"With the tremendous recent success of films such as The Avengers, Thor and the Batman series of films, this feels like the best time to tackle that dream. Best of all, unlike many other start-up ventures, I'm not looking to get into these areas, I'm already working in them; now it's just a matter of taking the next logical step: consolidation."
The writer is currently working on DC Comics' Before Watchmen miniseries Nite Owl and Doctor Manhattan, and the sequel to his Superman: Earth One graphic novel.
Joe's Comics will launch in spring 2013.