Marie Harriet Brenner was born in San Antonio, Texas to Milton and Thelma Brenner. She grew up in San Antonio and moved to New York in 1970.

Her father was chairman of Solo Serve Corporation, a chain of Texas discount stores started by her grandfather Isidor Brenner, who emigrated from Mexico to Texas during the Mexican Revolution.

She is the niece of Anita Brenner, anthropologist and author of Idols Behind Alters, published in 1929. Anita was a member of the circle of Mexican muralists and artists, Diego Rivera, Frida Kahlo, Edward Weston and Tina Modotti, who flourished in Mexico in the 1920s and was widely credited with helping to introduce their work in the United States. One of the first women to be a regular contributor toThe New York Times, Anita Brenner once interviewed Leon Trotsky, the deposed leader of the Russian Revolution and was an authority on Mexico and Latin American affairs.

She had an older brother Carl, a lawyer turned apple farmer who was the focus of her memoir, Apples and Oranges: My Brother and Me, Lost and Found.

Brenner earned a Bachelor of Fine Arts from the University of Texas at Austin and received a M.A. from New York University Film School. She was the first female baseball columnist covering the American League, traveling with the Boston Red Sox for the Boston Herald during the 1979 season.

Brenner worked as a contributing editor for New York from 1980—1984, and covered the Royal Wedding of Prince Charles and Lady Diana Spencer.

Brenner joined Vanity Fair as a special correspondent in 1984. She left the magazine in 1992 to become a staff writer at The New Yorker, returning to Vanity Fair in 1995 as writer-at-large.

Her explosive 1996 article for Vanity Fair on Jeffrey Wigand and the tobacco wars, titled "The Man Who Knew Too Much" was made into the 1999 feature film The Insider, starring Russell Crowe and Al Pacino, and directed by Michael Mann. It was nominated for seven Academy Awards, including Best Picture.

Brenner's 2002 Vanity Fair article, "The Enron Wars," delving into the investigation into the Enron scandals made national news when Senator Peter Fitzgerald used it to question witnesses testifying before a senate committee.

An archive of Brenner's work is stored at the Howard Gotlieb Archival Research Center at Boston University.

In 2009, the Manhattan Theater Club announced that it had commissioned Alfred Uhry to adapt Brenner's memoir Apples and Oranges: My Brother and Me, Lost and Found for the stage.