Berger majored in English literature and art history at Brooklyn College, and upon her graduation in 1979, she entered the comics profession as an assistant to editor Paul Levitz at DC. She later became Levitz's editor when he was writing Legion of Super-Heroes. More interested in horror comics, she soon became editor of House of Mystery, and was instrumental in nurturing Alan Moore's Swamp Thing book, taking over the editing from co-creator Len Wein. She also edited Amethyst, Princess of Gemworld. She later helped bring Neil Gaiman's work to a mass audience by having him write The Sandman.

The success of these titles, and her willingness to help the writers who worked with her push the envelope of what could be done in mass-circulation comic books, led to the creation of the mature-reader Vertigo line in 1993.

Berger is married to fellow DC employee Richard Bruning.

In 2007 Berger was named supervising editor (along with Senior Editor Shelly Bond) of Minx, a new comic book imprint published by DC. Minx published comics and graphic novels aimed at teenage girls until they were cancelled in 2008.

Berger won the Inkpot Award in 1990, three Eisner Awards (1992, 1994 and 1995), and the Comics Buyer's Guide Award for Favorite Editor every year from 1997 through 2005.