In the summer of 2000, Somerhalder starred in the short-lived WB series Young Americans, a spin-off of Dawson’s Creek. He played Hamilton Fleming, the son of the dean of a prestigious boarding school. In 2002, Somerhalder played bisexual character Paul Denton in Roger Avary’s adaptation of Bret Easton Ellis’ novel, The Rules of Attraction, alongside James Van Der Beek, Shannyn Sossamon, and Jessica Biel.

In 2004, Somerhalder scored his breakthrough role when he played Boone Carlyle in the hit TV show Lost. Despite his character’s death in the twentieth episode of the first season, Somerhalder returned to the role of Boone for seven more episodes between 2005 and 2010, including the series finale. Somerhalder was the first major character to die.

In 2009, Somerhalder appeared in the movie The Tournament where he played the role of an assassin participating in a lethal competition with other assassins. He appears in the coffee table book About Face by celebrity photographer John Russo.

In June 2009, Somerhalder was cast in the role of Vampire Damon Salvatore as a series regular in The CW television drama series The Vampire Diaries. The series premiere attracted The CW’s highest premiere ratings of any season premiere since the network began in 2006. The series has continued to be the highest-rated series on its channel with both Somerhalder’s performance and the show receiving a positive response from critics. Somerhalder began directing The Vampire Diaries in its third season and produced the series at the start of season 8. Somerhalder has received several Teen Choice Award’s and a People’s Choice Award for his participation on the series.

Somerhalder was involved in the cleanup after the Deepwater Horizon oil drilling disaster on April 22, 2010. His efforts included cleaning of oiled wildlife and taping public service announcements to let the public know how they could help. Somerhalder also supports the St. Tammany Humane Society, an organization for animal shelter and welfare. On November 13, 2010, he hosted a Bash on the Bayou charity fundraiser for the Society. During the event, Somerhalder was presented with a donation of $11,100 by The Vampire Diaries fandom for his birthday project.

On December 8, 2010, Somerhalder’s 32nd birthday, he launched the “Ian Somerhalder Foundation” which he hopes will educate people on the importance of protecting the environment and animals: “Instead of gifts this year, my birthday wish is that we come together and raise funds to support projects that protect our habitat and nurture our furry friends. He opposes GMO foods and factory farming, and supports ecologist Allan Savory in his crusade to let cows graze in sync with nature to enrich soil, enhance biodiversity, and reverse climate change. In 2011 Somerhalder visited Savory in Africa and announced he was making a documentary about him with the goal of winning him a Nobel Prize.

In October 2012, Somerhalder was cast in the film Time Framed, which had begun filming in Los Angeles. In April 2018, Somerhalder was cast in the role of Dr. Luther Swann as a series regular in the Netflix science fiction horror series V Wars. The series premiered on Netflix on December 5, 2019 and was cancelled in March 2020.

In mid-2014, Somerhalder began dating actress Nikki Reed. They confirmed their engagement in February 2015 and married on April 26, 2015, in Malibu, California. Their daughter, Bodhi Soleil was born on July 25, 2017.