He played Brad Colbert in the miniseries Generation Kill (2008), and had his breakthrough portraying vampire Eric Northman in the television series True Blood (2008–2014).

[9] In 1989, his lead role in the Swedish television production Hunden som log (The Dog That Smiled) earned him praise and brought him to prominence in Sweden at age 13.

He served in the Swedish Navy's SäkJakt ("protect and hunt") unit that dealt with anti-sabotage and anti-terrorism in the Stockholm archipelago, for 18 months.

An adaptation of journalist Evan Wright's book of the same name, Generation Kill follows the 1st Reconnaissance Battalion of the United States Marine Corps during the early part of the Iraq War.

[19] Though initially reluctant about playing a vampire, he sent an audition tape for the role of Bill Compton on learning that screenwriter Alan Ball was behind the project.

[25][26] Skarsgård appeared on the cover of the September 2010 issue of Rolling Stone with his True Blood co-stars Anna Paquin and Stephen Moyer.

The remake's director, Rod Lurie, transferred the small town setting from Cornwall to Mississippi and described Venner as "an ex-football star gone to seed".

[12] In 2012, Skarsgård appeared alongside Taylor Kitsch and Rihanna in Peter Berg's Battleship, an adaptation of the Hasbro game.

[21][31] He also appeared alongside Julianne Moore and Steve Coogan in Scott McGehee and David Siegel's film What Maisie Knew, an adaptation of the Henry James novel of the same name.

In addition to being intentional about finding nuances in the character's predatory quality, Skarsgård admitted his excitement about playing the role "without justifying or condoning" his behavior.

[36] From 2017 to 2019, Skarsgård starred in the drama series Big Little Lies as Perry Wright, an abusive husband to Nicole Kidman's character, Celeste.

[41] Reviewing the first-season finale, The Hollywood Reporter's Daniel Fienberg found Skarsgård's performance "utterly chilling".

[42] Skarsgård won the Primetime Emmy Award for Outstanding Supporting Actor in a Limited Series or Movie in 2017 for the role.

Critics were fond of the film, with The Guardian's Kristy Puchko commending Skarsgård in the minor role and how he "makes a meal out of it".

[49] Skarsgård starred in The Stand, a CBS All Access miniseries based on the 1978 novel of the same name by Stephen King, portraying Randall Flagg, a charming demon.

[59] In 2023, Skarsgård starred in the thriller Infinity Pool,[60] and returned as Lukas Matsson for the fourth and final season of Succession.

[61][62] For his role as Matsson, Skarsgård was nominated for the Primetime Emmy Award for Outstanding Supporting Actor in a Drama Series in 2023.

A few days into the trek, it was decided that the competition part would be cancelled due to hazardous terrain and weather conditions, so the teams combined forces and continued together, and all three successfully reached the South Pole on 13 December 2013.