Editor
In 1974, Jones started her professional comic book career at Warren Publishing. She went from assistant to senior editor of the comics line (Creepy, Eerie, and Vampirella) before leaving the company at the end of 1979.
In January 1980, she joined Marvel Comics, where she initially worked again as an editor, most notably on Uncanny X-Men, which she edited for almost four years (#137–182). Simonson (as "Louise Jones") edited another X-Men spin-off, The New Mutants (vol. 1), at its debut in 1983 (after leaving the book, she would have a "cameo" in New Mutants #21, drawn in as a slumber party guest by artist Bill Sienkiewicz). During this period, she also edited Marvel's Star Wars and Indiana Jones comics.
Writer
At the end of 1983, she quit her editing job at Marvel to try her hand at full time writing as Louise Simonson. She created the Eagle Award-winning Power Pack. The title, which debuted in August 1984, featured the adventures of four pre-teen superheroes. Simonson would write the majority of the title's first forty issues, even coloring one issue (#18). Her other Marvel writing work included Starriors, Marvel Team-Up, Web of Spider-Man, and Red Sonja.
In 1986, Simonson began a long stint as writer of X-Men spin-off X-Factor. In #6, her first issue, she and artist Jackson Guice introduced Apocalypse, a character who would go on to play a major role in the X-Men franchise. From #10 of the title, she was joined by her husband, Walt Simonson, on pencils. In #25, the creators gave the character Angel blue skin and metal wings in a process which would lead to his being renamed as Archangel. Her run on X-Factor included the story arcs "Mutant Massacre", "Fall of the Mutants," and "Inferno". She ended her run on the title with #64 in 1991.
In 1987, beginning with issue #55, she became the New Mutants scripter, writing it for three and a half years until #97 in 1991. It was during this run that she and artist Rob Liefeld introduced Cable, another important character in the X-Men franchise. Louise also helped her husband Walt Simonson color his 1983 Marvel graphic novel Star Slammers.
In 1988-89, she and her husband co-wrote the critically acclaimed Havok and Wolverine: Meltdown limited series painted by Jon J Muth and Kent Williams
In 1991, Simonson began writing for DC Comics. She, artist Jon Bogdanove, and editor Mike Carlin launched a new Superman title, The Man of Steel ... a title she would write for eight years until #86 in 1999. During this run, Simonson (along with Carlin, Dan Jurgens, Roger Stern and others) was one of the chief architects of The Death of Superman storyline, in which Superman died and was resurrected. It was during that story, in Superman: The Man of Steel #19, that Simonson and Bogdanove introduced their character Steel, who graduated to his own title in 1993, with Simonson as writer until #31. The character went on to feature in an eponymous feature film starring Shaquille O'Neal in 1997.
In 1999, Simonson returned to Marvel to write a Warlock series, which featured a character from her previous New Mutants run. Also at Marvel that year, she wrote a miniseries, Galactus the Devourer, in which Galactus died temporarily.
In 2005, she wrote stories featuring Magnus Robot Fighter for the publisher ibooks.
In 2007, Simonson wrote a one-shot starring Magik of the New Mutants as part of a four-issue event known as Mystic Arcana.
In 2008-2009 she wrote several issues of Marvel Adventures. She also co-wrote the comic World of Warcraft, based on the multi-million player internet game, for Wildstorm, and a manga story, based in the Warcraft universe, for Tokyopo.
From 1993 through 2009, she also wrote five picture books and eleven novels for middle-readers, many of which featured characters from DC Comics. Two YA novels, Wonder Woman: The Gauntlet and Wild at Heart, published by Bantam Books, were based on the Justice League cartoon. She also wrote an adult Batman novel and the non-fiction DC Comics Covergirls, published by Rizzoli.