Peyser's parents, Austrian-born Ruth (née Sophie Staendig) and German-born mathematician Gideon Peyser, met while serving in the Israeli army. They settled in New York City in the 1950s. Andrea grew up in Queens, with an older sister, Rhona (who died in 2002) and graduated from Bayside High School. She attended the State University of New York at New Paltz and Albany.
Peyser's first job in journalism after graduating from college was a temporary assignment for the Albany, New York, bureau of the Associated Press. She then moved to the West Virginia bureau, followed by a brief time at CNN, and then moved to The Tampa Tribune.
Peyser was hired by the New York Post in 1989, and became a columnist after her coverage of an alleged sex scandal concerning the New York Mets during spring training in the early 1990s. In 1995 she released, "Mother Love, Deadly Love: The Susan Smith Murders'' (HarperCollins).
The Washington Post has described Peyser as an "object of fascination among some media observers in New York, who count her unforgiving, exuberantly spiteful columns as a guilty pleasure." New York magazine described her as "the Madame Defarge of the New York Post" in a 2004 profile.
Her 2002 column titled "The confessions of the Jogger 5 do not lie" appears in the Ken Burns documentary The Central Park Five. The convictions of the five juveniles who confessed in the 1989 Central Park jogger case were vacated after another man's confession was substantiated by DNA evidence.
In 2009, she came out with "Celebutards: The Hollywood Hacks, Limousine Liberals and Pandering Politicians Who Are Destroying America through the publisher, Kensington.
In October 2001, Peyser's employer, New York Post owner Rupert Murdoch, offered a rare personal apology over Peyser's reference to CNN correspondent Christiane Amanpour in a September 21 column as a “CNN war slut”.
In May 2012, The Observer and New York magazine noted that in eight years she has celebrated the possibility of nine different people getting raped in jail.
In December 2013, Peyser was criticized for her commentary on the state funeral of Nelson Mandela. In her column, Peyser wrote that President Obama behaved like a "hormone-ravaged frat boy on a road trip to a strip bar". She concluded by saying that President Obama "has some 'splaining to do", an expression of Ricky Ricardo from the I Love Lucy show.
She is married to Mark D. Phillips, a photojournalist and website designer. They have a daughter, Eliza, and live in Brooklyn.