Carla Cohen, after losing her job with the Carter administration, decided to create an independent bookstore in Washington, D.C., despite having no previous experience with running a business.

[3] Meade worried that the name was a put-off, and the store struggled at first to attract authors to speak at its events and relied on local journalists to publicize the location.

[2][5] Business continued to be successful during the late 1990s as other independent bookstores fell by the wayside and companies such as Barnes & Noble expanded.

[6] Cohen and Meade set him up in a part-time position to see how he would interact with the employees and sold him an equity stake in the business without informing the other staff members.

[2][12] It was announced on March 28, 2011 that two former employees of The Washington Post, Lissa Muscatine, and her husband, Bradley Graham, had purchased the store from Meade and David Cohen.

[18] Politics & Prose announced plans for a third location to open in October 2017 at The Wharf, a new development at the Southwest Waterfront.

[22] The owners of Politics and Prose initially hired attorneys from Jones Day, which local DC news outlet DCist described as, "known for its aggressive anti-union tactics" to fight the unionization effort.

[27] The Washington Post notes that as the talks gained prominence and the store grew more popular, Cohen and Meade, the original co-owners, "became known as literary tastemakers".

[9][27] Famous readers at its author events have included politicians such as Presidents Bill Clinton and Barack Obama, UK statesman Boris Johnson, and former Senator Edward Brooke, as well as authors J.K. Rowling, Salman Rushdie, and Amy Chua, photographer Annie Leibovitz, and investigative reporter David Halberstam.

[27][30][31][32][33] Cohen in the past refused to allow prominent writers to appear in the store, such as Matt Drudge, ostensibly because of their conservative leanings.

[2][34] Politics and Prose is often seen to be an important stop for authors publicizing their work and is regarded as being a significant part of DC culture.