She was the guest star in the second episode of the long running NBC television series Law & Order.
She played the role of an agoraphobic woman in a February 1993 episode of Murder, She Wrote titled, "Threshold of Fear".
She reprised the role for the 2004 sequel, Tanner on Tanner.
playing several characters after it came to Broadway in 1989.
In 2002, she also landed a role in the indie comedy Igby Goes Down, and her turn in the theatrical production of Clare Boothe Luce's play The Women was captured for PBS' Stage on Screen series.
Post-Sex in the City, Nixon made a guest appearance on ER in 2005, as a mother who undergoes a tricky procedure to lessen the effects of a debilitating stroke.
She received critical acclaim for both performances, especially for the latter, which many considered as "Oscar-worthy".She reprised the role in the films Sex and the City (2008) and Sex and the City 2 (2010).Other film credits include Amadeus (1984), The Pelican Brief (1993), Little Manhattan (2005), 5 Flights Up (2014), James White (2015), and playing Emily Dickinson in A Quiet Passion (2016).In 2012, Nixon starred as Professor Vivian Bearing in the Broadway debut of Margaret Edson's Pulitzer Prize–winning play Wit.Produced by the Manhattan Theatre Club, the play opened January 26, 2012 at the Samuel J. In 2012, Nixon also starred as Petranilla in the TV miniseries of Ken Follett's World Without End broadcast on the Reelz Channel, alongside Ben Chaplin, Peter Firth, Charlotte Riley and Miranda Richardson.
She won the 2006 Tony Award for Best Actress in a Play for Rabbit Hole, the 2008 Primetime Emmy Award for Outstanding Guest Actress in a Drama Series for Law & Order: Special Victims Unit, the 2009 Grammy Award for Best Spoken Word Album for An Inconvenient Truth, and the 2017 Tony Award for Best Featured Actress in a Play for The Little Foxes.