Janney was born in Dayton, Ohio, the daughter of Macy (née Putnam), a former actress and homemaker, and Jervis Spencer Janney, Jr., a real estate developer and jazz musician. She has two older brothers, Jay and Hal. She attended The Miami Valley School in Dayton, where she was named a distinguished alumna in 2004, and the Hotchkiss School in Connecticut. She then attended Kenyon College. At Kenyon, Janney studied under another Kenyon alum, Paul Newman. She went on to study drama at the Neighborhood Playhouse in New York and the Royal Academy of Dramatic Art in London. She attended The Neighborhood Playhouse the same years as actor Dylan McDermott.
Janney's first roles on television were as comedic foils on soap operas: she first played Vi Kaminski for a short time on As the World Turns, following up with a two-year stint as one of the Spaulding maids, Ginger on Guiding Light. In the spring of 1994, she appeared in the season finale of Law & Order, as a reluctant witness against a member of the Russian mob.
Janney has appeared in a number of films with roles of various sizes, including the 1990s films American Beauty, The Object of My Affection, Big Night, The Impostors, Drop Dead Gorgeous, The Ice Storm, Primary Colors, 10 Things I Hate about You, and Private Parts, and the 2000s films Nurse Betty, The Hours, The Chumscrubber, How to Deal, Winter Solstice and a considerable role in the animated movie, Finding Nemo, voicing Peach, the starfish. In 2006, Janney carried notable roles in the movies, Margaret and Over the Hedge, an animated comedy.
In 1999, she was cast in the role of presidential press secretary C.J. Cregg on the television drama The West Wing, for which she eventually won four Emmy Awards. Two of the Emmys were for Primetime Emmy Award for Outstanding Supporting Actress - Drama Series in 2000 and 2001, and two were for Primetime Emmy Award for Outstanding Lead Actress - Drama Series in the years 2002 and 2004. She was also nominated for Outstanding Lead Actress in a Drama Series in the 2003 and 2006 Primetime Emmys. She is one of six cast members from The West Wing to have won an Emmy for their work - however, Janney is the only one who has won more than once. Janney also won two Screen Actor's Guild awards for Best Actress in a dramatic series, in 2001 and 2002, for her portrayal of C.J Cregg. The cast of "The West Wing" won the Screen Actor's Guild award for Best Ensemble in a dramatic series the same two years. Additional accolades for Janney's work in "The West Wing" include four Golden Globe award nominations, and a nomination in 2002 for American Film Institute's Actor of the Year.
Weekend trips to Washington, D.C. were frequently a part of Janney's schedule, and for the rest of the cast as well, as many outdoor scenes on The West Wing were actually filmed in the nation's capital. Janney also met several times with former White House Press Secretary Dee Dee Myers who served in the Clinton Administration from 1993–1994. Janney met with Myers in New York City to help portray her character more authentically.
Janney at the 2007 Toronto International Film Festival
The West Wing concluded in January 2006, and the last episode aired in May of that year. Even though the latter seasons were plagued by declining ratings, the overall rating of Janney remained a relatively positive one, touted by Entertainment Weekly as "one to watch", "uncommonly beautiful and infinitely expressive". In January 2006, West Wing's cast was also nominated by the Screen Actors Guild for Outstanding Performance by an Ensemble Cast. Janney, Martin Sheen, Bradley Whitford, Janel Moloney, and other members of the cast appeared at the SAG Awards to honor their late cast mate and friend, John Spencer.
In 2006, she was nominated for an Independent Spirit Award for her performance in the film Our Very Own. Many of Janney's long time friends were involved with Our Very Own including its producer Shannon Mc