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Adams began her career as a dancer in dinner theatre, a pursuit she followed from 1994 to 1998. They made her film debut with a supporting part in the dark comedy Drop Dead Gorgeous (1999). She made guest appearances on television and took on roles as the "mean girl" in low-budget feature films. Her first major role was in Steven Spielberg's biopic Catch Me If You Can (2002), but she was unemployed for a year afterwards. Her breakthrough came when she portrayed a loquacious pregnant woman in the independent comedy-drama Junebug(2005), for which she received her first Academy Award nomination.

The musical fantasy film Enchanted (2007), in which Adams played a cheerful princess-to-be, marked her first success in a leading role. She followed it by playing other naïve, optimistic women in films like the drama Doubt (2008). Subsequently, she played more assertive parts, earning positive reviews, in the sports film The Fighter (2010) and the psychological drama The Master (2012). From 2013 to 2017, she portrayed Lois Lane in superhero films set in the DC Extended Universe. She won two consecutive Golden Globe Awards for Best Actress for playing a seductive con artist in the crime film American Hustle (2013) and painter Margaret Keane in the biopic Big Eyes (2014). Further acclaim came for playing a linguist in the science fiction film Arrival (2016), a self-harming reporter in the HBO miniseries Sharp Objects (2018), and Lynne Cheney in the satire Vice (2018).

Adams' stage roles include the 2012 revival of Into the Woods at the Public Theatre and the 2022 West End revival of The Glass Menagerie. In 2014, she was named one of the 100 most influential people in the world by Time and featured in the Forbes Celebrity 100 list.