Orth attended the University of California, Berkeley, graduating in 1964. Following her graduation from college, she served in the Peace Corps in Medellín, Colombia, from 1964 to 1966.

Orth began her career as the third female writer at Newsweek where she wrote seven cover stories. In 1981 she was the principal correspondent of Newsweek Woman on Lifetime TV. From 1983 to 1984 she was a network correspondent for NBC News.

Orth was a contributing editor at Vogue from 1984 to 1989 and a columnist for New York Woman from 1986 to 1990.

Orth has written for Vanity Fair since 1988 and has been a special correspondent for that magazine since 1993. Among the heads of state she has interviewed are Russian President Vladimir Putin, British Prime Minister Margaret Thatcher, Argentinian President Carlos Menem, and Irish President Mary Robinson. Right after 9/11 she traveled to Central Asia to investigate the connection between drugs and terrorism for "Afghanistan's Deadly Habit."

Orth reported on alleged molestation charges brought by then minor Jordan Chandler against Michael Jackson in 1993, which was ultimately settled between Jackson's insurance company and the Chandlers. Orth subsequently reported for the magazine on Jackson four more times, including articles on Jackson's appearance on ABC News's PrimeTime Live, on a civil lawsuit filed against him in 2003 by concert promoter Marcel Avram, and on the criminal suit brought against Jackson in 2004, again for child molestation which he was acquitted.

Orth then investigated pedophile priest Paul Shanley. Orth has also written articles on Madonna, Tina Turner, Karl Lagerfeld and Conrad Black. Orth recently profiled France's First Lady Carla Bruni and detailed the inside story of "Inside Colombia's Hostage War" in the November 2008 Vanity Fair.

Orth then authored the best selling book "Vulgar Favors: Andrew Cunanan, Gianni Versace and the Largest Failed Manhunt in U.S. History" and "The Importance of Being Famous", a collection of her pieces from Vanity Fair articles with updates and commentary.

Orth was named by Newsweek as one of the "Overclass 100," and won a National Magazine Award for group coverage of the arts. She was also nominated for a National Magazine Award for her story on Arianna and Michael Huffington, "Arianna's tk", for Vanity Fair in 1994.

Orth was a Peace Corps volunteer in Medellín, Colombia, where she helped build Escuela Marina Orth. In 2004 the Secretary of Education asked her to help make her school the first public bilingual school in Colombia. It is now the first school in Colombia with the One Laptop Per Child project. Since then she has formed two foundations...K12 Wired in the U.S. and Fundacion Marina Orth in Colombia. The non profit foundations were formed to create a model program that teaches English and information technology in Escuela Marina Orth, with hope that one day the programs can be expanded to other schools throughout the country. In addition, she is currently working with the Colombian Coffee Growers Federation and the city of Medellin to institute a new program for former Colombia Peace Corps volunteers to return to Colombia for limited periods of time. Its first group arrived in Colombia in September 2008.

She has written extensively on FARC, the Colombian guerrilla group.

Maureen Orth lives in Washington, D.C. In 1983 Orth married the political journalist Tim Russert, whom she met at the 1980 Democratic National Convention. Tim Russert was the Washington bureau chief of NBC News and moderator of Meet the Press when he died on June 13, 2008. Their son, Luke Russert, who was born in August 1985, is an NBC News correspondent.

Orth is the dedicatee of her friend Larry McMurtry's Pulitzer Prize-winning novel Lonesome Dove.