Clarkson was born in New Orleans, Louisiana, the daughter of Jacquelyn (née Brechtel), a prominent local New Orleans politician and councilwoman, and Arthur, a school administrator who worked at the Department of Medicine of Louisiana State University. Clarkson's great-grandfather was from Barcelona, Spain. Clarkson studied drama at Fordham University, where she graduated summa cum laude, and earned her MFA at the Yale School of Drama before making her film debut in The Untouchables in 1987.

Clarkson's Broadway theatre credits include The House of Blue Leaves and Eastern Standard.

Clarkson had supporting roles in a series of high-profile films in her early career. Her first movie role, at age 27, was as Elliot Ness's (played by Kevin Costner) wife in The Untouchables. She was also featured in The Dead Pool, Rocket Gibraltar and Everybody's All-American. She starred in the short-run television series Davis Rules, and in the miniseries Alex Haley's Queen. More often a character actor than a leading woman, she has also appeared in such major films as The Green Mile (1999), Far from Heaven (2002) and Good Night, and Good Luck (2005). Her breakout role which put her on the indie film map, was High Art (1998) where her role as Greta, a German drug addicted lesbian former model, got rave reviews.

In 2002, she originated her role as Sarah O'Connor (a.k.a. "Aunt Sarah") in HBO's Six Feet Under. She went on to win an Emmy for Outstanding Guest Actress that year for her performance, a feat she repeated for the same role in 2006.

In 2003, she gained critical acclaim and a Special Jury Prize for her work in four films that debuted at the Sundance Film Festival : All the Real Girls, The Baroness and the Pig, The Station Agent and Pieces of April. Later that year, she was nominated for an Academy Award for Best Supporting Actress for Pieces of April, in which she plays an acerbic mother dying of cancer.

In 2006, she portrayed Sadie Burke, in All the King's Men, set in her native New Orleans. In 2008, she had supporting roles in Elegy, as a womanizer's put-upon girlfriend, and Woody Allen's Vicky Cristina Barcelona as an unhappily-married housewife.

Clarkson returned to New Orleans for 2009 January 17 reopening of the Mahalia Jackson Theatre for the Performing Arts. She served as Master of Ceremonies for a gala celebration featuring Plácido Domingo in concert with the New Orleans Opera, conducted by Robert Lyall. She also made a cameo appearance in the Saturday Night Live Digital Short "Motherlover" on May 9, 2009. The video featured Andy Samberg, Justin Timberlake, and Susan Sarandon.

In 2010, she starred in Martin Scorsese's Shutter Island. Patricia was honored by the Jameson Dublin International Film Festival when she received one of the 2010 Volta awards for achievements in her career.

Sally Field (2001) · Patricia Clarkson (2002) · Alfre Woodard (2003) · Sharon Stone (2004) · Amanda Plummer (2005) · Patricia Clarkson (2006) · Leslie Caron (2007) · Cynthia Nixon (2008) · Ellen Burstyn (2009)

Complete list: (1974–2000) · (2001–present)