In 2016, Graham reprised her role on a Gilmore Girls Netflix revival miniseries A Year in the Life and published a memoir, Talking as Fast as I Can.

Her mother, Donna Grant, was a fashion buyer, and her father, Lawrence Graham, a candy industry lobbyist who was president of the National Confectioners Association.

[7] Graham was five years old when her parents divorced, and she moved to the Virginia suburbs of the Washington, DC metropolitan area with her father, who became a congressional staffer.

[9][13] As a girl, Graham rode horses competitively, but soon switched to acting,[14] honing her talent at Langley High School, where she took part in the drill team and graduated in 1984.

[17][18] After moving to Texas in 1992, Graham earned a Master of Fine Arts degree in Acting Performance from Southern Methodist University.

[19] After completing her education, Graham moved back to New York City where she worked as a waitress and as a tutor teaching SAT test prep for The Princeton Review.

[9][17] While she aspired to become an actress, she made publicity appearances wearing the costume of Striker, the dog mascot of the US-based 1994 FIFA World Cup.

She appeared in various commercials for products such as Cascade dishwasher detergent,[20] Dimetapp, AT&T and Lean Cuisine and hosted free preview weekends on The Movie Channel.

In 2000, Graham landed her breakthrough role on Gilmore Girls as Lorelai Gilmore—a witty "thirty-something" raising her teenage daughter in small-town Connecticut.

[32] Graham also worked as the voice-over announcer in national advertising for Kellogg's various Special K products in 2007, and for American Express ads in 2008 introducing the Plum Card, which targets small and growing businesses.

[33] Graham made her Broadway debut as Miss Adelaide in the revival of Guys and Dolls, which began preview performances at the Nederlander Theatre on February 5, 2009, and opened on March 1, 2009.

[36][37] In September 2009, Graham voiced the character Fran Lockwood, Flint's late mother, in the Sony Pictures Animation film Cloudy with a Chance of Meatballs.

In October 2009, it was announced that Graham would replace Maura Tierney in the television series Parenthood as single mother Sarah Braverman.

In 2015, Graham appeared in the adventure drama film Max, playing the mother of an American marine killed in Afghanistan who subsequently adopts his Malinois dog.

In October 2016, Graham appeared in Middle School: The Worst Years of My Life, playing the mother of Griffin Gluck's character.

As a result of her own distaste for parts of her youth, Graham related to the title, sparking her initial interest in participating.

In 2024, Graham and Aisling Franciosi were cast opposite Dylan O'Brien and James Sweeney in David Permut's movie Twinless.

[62][63] Graham has appeared on the cover of numerous magazines, including Health, More,[64] Self, Seventeen,[65] Entertainment Weekly,[66] Redbook,[67] Good Housekeeping, Ladies' Home Journal, and Parade.

[75] Graham's Don't Worry About It focuses on "advice for graduates and reflections on staying true to yourself" and was her third New York Times best seller.