Wentworth was born in Washington, D.C. to a prominent family. Her mother, Mabel "Muffie" Brandon Cabot (née Hobart), was Nancy Reagan's White House Social Secretary from 1981 to 1983. Her father, Eric Wentworth, was a reporter for The Washington Post. Her stepfather, Henry Brandon, was the editor of the London Sunday Times. Her maternal grandmother was explorer Janet Elliott Wulsin (1894–1963).
She attended the Dana Hall School for Girls in Wellesley, Massachusetts. She is a graduate of Bard College in Annandale-on-Hudson, New York.
Wentworth was a cast member on the Fox sketch comedy series In Living Color from 1992 to 1994, where she was known for impressions of Cher, Amy Fisher, Hillary Clinton, Princess Diana, Brooke Shields, Lisa Marie Presley, Sharon Stone, and others. She has also made correspondent appearances on The Tonight Show with Jay Leno and The Oprah Winfrey Show. In 1995, she played Jerry'sgirlfriend Sheila ("Schmoopie") in the famous "Soup Nazi" episode of Seinfeld. She also had a recurring role as the title character's boss on the WB series Felicity. In 2003, she co-hosted the syndicated talk show Living It Up! With Ali & Jack, with Jack Ford.
She starred in the comedy Head Case on the Starz TV network. She guest starred on the NBC show The Marriage Ref.
Wentworth hosts Daily Shot, a short daily talk show segment on Yahoo! Shine.
Wentworth is married to George Stephanopoulos, ABC News Chief Anchor and former political adviser to the Clinton administration. The two met on a blind date in April 2001, were engaged two months later, and were married on November 20, 2001, at the Archdiocesan Cathedral of the Holy Trinity on New York City's Upper East Side. They have two daughters: Elliott Anastasia Stephanopoulos (September 9, 2002) and Harper Andrea Stephanopoulos (June 2, 2005).
Some people say you can tell a lot about a person by the look of her home. I sincerely hope that's not true. If it is, I've got multiple-personality disorder. In the past ten years, I have moved six times. Each relocation has resulted in a complete reinvention of my surroundings, from neutral linens and bohemian block prints in Los Angeles to nailheaded furniture and bold colors like eggplant in Manhattan. So when my husband, George Stephanopoulos, host of ABC's Sunday news program This Week, and I settled in Washington, D.C., a few years ago with all the seashells I'd been collecting since childhood, I found myself faced with a Colonial Revival house in Georgetown and a palette trained in Hollywood. More important, how could my fragile branches of Pacific coral survive a house full of kids?
To answer this and other pressing domestic questions, I called my style shrink, interior designer Elizabeth Martin. My roommate in boarding school, she had transformed our 12-foot-square dorm room into a Paris-style pied-à-terre. This time around, Beth did what any friend with a passion for Oly furniture and David Hicks textiles would do—grabbed her swatches and jumped on a plane.