Born in El Paso, Texas, she was raised in the small town of Alpine in the west of the state. She went on to study English Literature in St. Edward's University in Austin. While an employee of the University of Texas at Austin, she began a blog called Mouse Words, which focused on both music and feminism. Having won the Koufax award for Best New Blog of 2004 for her work on the site, she began to write for the popular weblog Pandagon, one of the first feminist blogs. She has written about political differences with her small-town family. Recently she moved to New York.

On January 30, 2007, the John Edwards 2008 presidential campaign hired Marcotte to act as the campaign's blogmaster. Soon afterward, many bloggers began to quote Marcotte's blog, especially posts in which she attacked the Catholic Church's position on birth control and access to abortion. Columnist Kathryn Jean Lopez wrote, "Her hostility to religion and in particular the Catholic Church should alarm Edwards." Journalist Terry Moran wrote, on an ABC News blog, "her comments about other people's faiths could well be construed as hate speech."

Marcotte's most outspoken critic was Bill Donohue of the Catholic League, who publicly demanded that the Edwards campaign terminate Marcotte's appointment, claiming that she was anti-Catholic. An Edwards campaign press release on Thursday, February 8, 2007 stated that while Edwards was "personally offended" by some of what Marcotte wrote, her job as the campaign blogmaster was secure.

On February 12, 2007, the Catholic League denounced Marcotte's review of the film Children of Men as "anti-Christian". Later that day, Marcotte announced that she had resigned from the Edwards campaign, and accused Donohue of a sexist perspective in the calls for her resignation. The campaign accepted her resignation. She returned to her work on other blogs.

In 2008, Marcotte published her first book, entitled It's a Jungle Out There: The Feminist Survival Guide to Politically Inhospitable Environments. It's a jungle out there : the feminist survival guide to politically inhospitable environments [WorldCat.org] Jill Filipovic of AlterNet described the book as a "how-to manual for feminist-minded women to take on a sexist society and have a good laugh along the way." In August 2007, Marcotte posted an image of the chosen book cover on her blog; the image "was a retro-Hollywood pulp cover of a gorilla carrying a scantily clad woman." The image immediately came under fire for perpetuating racist tropes, and, consequently, Marcotte and Seal Press changed the cover image.

When the book was finally released, it again set off controversy in the feminist blogosphere for use of images that many saw as racist. To illustrate the volume, the publishers used images taken from the 1950s Joe Maneely comic, Lorna, the Jungle Girl, which was chosen for its retro comic art look. The illustrations used included stereotypical images of "savage" black Africans being beaten up by a white, blonde, superhero, described as "racist cartoons of 'natives' in a jungle setting." Marcotte subsequently issued an apology, adding that a second printing of It's A Jungle Out There will not contain illustrations.