After her parents divorced when she was two years old, Dern was largely brought up by her mother and maternal grandmother, Mary, who had Norwegian ancestry, from Oslo.

[11] At 16,[12] after doubling on her classes to graduate high school a semester early,[13] she sought and attained emancipation,[14] which allowed her to work the same number of hours as an adult on films.

Dern later enrolled at UCLA intending to double major in psychology and journalism, but withdrew two days into the semester to film Blue Velvet.

[15][13][16] In 1985, she was cast two weeks before production began as protagonist Connie Wyatt, a carefree 15-year-old girl who grabs the attention of a predatory stranger, in the film Smooth Talk.

[19] In the biographical drama film Mask, she played Diana Adams, a blind girl who becomes Rocky Dennis' love interest, starring alongside Eric Stoltz and Cher.

At the age of 17, she played Sandy Williams, one of the starring roles alongside Kyle MacLachlan and Isabella Rossellini, in the critically successful mystery thriller film Blue Velvet.

[23] Dern was cast for The Silence of the Lambs (1991), but lost the role due to studio's skepticism about her level of fame at the time.

[27][28] Dern played Ellie Sattler in Steven Spielberg's 1993 film Jurassic Park, achieving international recognition with the role.

[33][34][35] Ladd made a cameo appearance, playing her mother for the third time, following Rambling Rose and Wild At Heart, with Dern's character screaming a torrent of abuse at her.

Despite protests from people around her, she shrugged off concerns and immediately accepted the role,[36] where she received her third Primetime Emmy Award nomination for Outstanding Guest Actress In A Comedy Series.

[37] The decision significantly impacted her career in the following years with Dern revealing in an April 2007 airing of The Ellen DeGeneres Show that she did not work for more than a year and that she needed a "full security detail" following her appearance in the historic episode due to the resulting backlash at the time, but nevertheless called it an "extraordinary experience and opportunity" and "an incredible honor.

In Joe Johnston's biographical film October Sky, Dern played the teacher who is involved about amateur rocketry, launched by NASA engineer Homer Hickam (Jake Gyllenhaal).

In 2001, Dern reprised her role as Ellie in Jurassic Park III, which was directed by Johnston whom she had worked with in October Sky.

She starred in Mike White's directorial debut film Year of the Dog, alongside Molly Shannon, John C. Reilly and Peter Sarsgaard.

In 2008, Dern starred as Florida Secretary of State Katherine Harris in Recount, for which she won the Golden Globe Award for Best Supporting Actress – Series, Miniseries or Television Film.

[46] Dern played Amy Jellicoe, a "health and beauty executive who returns from a post-meltdown retreat to pick up the pieces of her broken life."

Dern brought screenwriter Mike White, whom she collaborated with on Year of the Dog, back into television work after he had suffered an on-the-job meltdown of his own.

Dern received her third Golden Globe Award and fifth nomination, her first in the Best Actress in a Television Series – Musical or Comedy category for her performance.

[50] In 2014, she co-starred alongside Reese Witherspoon in Jean-Marc Vallée's biographical drama film Wild portraying the character of Bobbi, mother of Cheryl Strayed in flashback scenes, for which she received her second Academy Award nomination and her first in the Best Supporting Actress category.

That same year, she portrayed Frannie Lancaster in the coming-of-age romance film The Fault In Our Stars and she portrays Beverly Ladouceur in the sports drama film When the Game Stands Tall directed by Thomas Carter, starring Jim Caviezel and produced by David Zelon for Mandalay Pictures.

[54][55][56] That same year, she collaborated for the fourth time with David Lynch, appearing as Diane Evans in the third season of the mystery serial drama television series Twin Peaks and joined the Star Wars franchise portraying Vice-Admiral Amilyn Holdo in Rian Johnson's space opera film Star Wars: The Last Jedi.

[60] Dern received her seventh Primetime Emmy nomination for the role in the category Outstanding Lead Actress In A Limited Series Or Movie.

[73] With Neill and Goldblum having led in their own Jurassic Park sequel, Trevorrow wanted Dominion to be Dern's film explaining, "It was important for the plot to be driven by Ellie.

[86] During the 66th Golden Globe Awards, on January 11, 2009, Dern expressed support for the incoming administration of Barack Obama during her acceptance speech for her Best Supporting Actress – Series, Miniseries or Television Film win, stating: "I will cherish this as a reminder of the extraordinary, incredible outpouring of people who demanded their voice be heard in this last election so we can look forward to amazing change in this country.

Dern received critical acclaim and was nominated for the Academy Award and Golden Globe for Best Actress for portraying the titular orphan in the drama Rambling Rose (1991).

[a] The following year, her performance in the television drama film Afterburn (1992) won her the Golden Globe and earned her a nomination for the Primetime Emmy Award for Outstanding Actress in a Miniseries or Movie.

Dern's performance of a dedicated mother in the HBO black comedy drama series Big Little Lies (2017–2019) was widely acclaimed.

The television drama film The Tale (2018) earned Dern nominations for the Critics' Choice, Golden Globe and Primetime Emmy Award for Outstanding Lead Actress in a Limited Series or Movie.