She also portrayed Melissa Chartres in The Last Man on Earth (2015–2018) and has starred in films such as American Wedding (2003), We Are Marshall (2006), The Boat That Rocked (2009), Unknown (2011), Seeking Justice (2011), and X-Men: First Class (2011).

[12] She has been on the covers of numerous international fashion magazines, including Interview, Allure, Rolling Stone, Town & Country, The Hollywood Reporter and W in the United States; Harper's Bazaar, Marie Claire, Tatler, Glamour and Red in the United Kingdom; Cosmopolitan in Germany; Grazia in Italy; and Tu Style and GQ in Italy.

In 2005, she appeared as a U.S. border guard's wife in the film The Three Burials of Melquiades Estrada, directed by and starring Tommy Lee Jones.

[14] She also appeared in the AMC original television drama series Mad Men for seven seasons as young suburban housewife and mother Betty Draper Francis.

She played a con artist in the Law & Order episode "Quit Claim" who, as a lone surviving suspect connected to a real estate scam involving organized crime, frustrates the efforts of Assistant District Attorney Michael Cutter to convict her.

[19] On November 14, 2009, Jones hosted an episode of Saturday Night Live, which featured musical guest The Black Eyed Peas.

[23][24] In 2019, she joined the cast of Netflix's comedy-drama series The Politician, playing the role of a bored and rich housewife Lizbeth Sloan.

[25][26] In 2020, Jones joined the cast of the Netflix series Spinning Out as Carol Baker, a former figure skater and a single mother who suffers from bipolar disorder.

[31] She served food with fellow actress Malin Åkerman at the Los Angeles Mission's annual Thanksgiving event on November 24, 2021.