Thor - The Avengers - Pirates of the Caribbean - King Arthur - The Hunt for Red October

Skarsgård started his acting career early; and, by the age of 21, his experience in film, TV, and stage was considerable. Most of his early roles were in Swedish television (such as Bombi Bitt) and films. Of Skarsgård’s work in the Swedish film, he is perhaps best known for Good Evening, Mr. Wallenberg, where he portrays Swedish diplomat Raoul Wallenberg, who worked to save Holocaust victims.

Skarsgård is particularly associated with director Lars von Trier and has appeared in six of the Danish auteur's features: The Kingdom, Breaking the Waves, Dancer in the Dark, Dogville, Melancholia, and Nymphomaniac. His most personal working relationship, however, is with Norwegian director Hans Petter Moland, who has directed the actor in Zero Kelvin, Aberdeen, In Order of Disappearance, and A Somewhat Gentle Man. Skarsgård considers Moland a close friend and, in 2009, he said of their relationship: "We're like an old married couple and I get separation anxiety." Another Scandinavian work that he is known for is the 1997 Norwegian film Insomnia, in which he plays the guilt-ridden policeman Jonas Engström.

Skarsgård’s first American film was the 1985 film Noon Wine, directed by Michael Fields, in which Skarsgård played a mentally-disturbed immigrant farmhand being chased by a bounty hunter. He acted opposite Fred Ward, who portrayed the farmer.^[5] In 1990, he starred in another American film, The Hunt for Red October, playing the character of Captain Tupolev, a Soviet submarine commander.

He was considered for the role of Oskar Schindler in Schindler's List. Skarsgård has said that people often mistook him for Liam Neeson, who portrayed Schindler in the film, and Skarsgård later replaced Neeson in the 2004 film Exorcist: The Beginning. He appeared as a guest star on the HBO TV Series Entourage, as Verner Vollstedt, the German director of the fictional film Smokejumpers, who has a bias against the main character Vincent Chase, one of the stars of the film. Skarsgård appeared as Bootstrap Bill Turner in both Pirates of the Caribbean: Dead Man's Chest and Pirates of the Caribbean: At World's End. In 2008, he starred as Bill Anderson in Universal Pictures' Mamma Mia! and reprised the role 10 years later in its sequel Mamma Mia! Here We Go Again.

Skarsgård played Dr. Erik Selvig in Marvel's 2011 film Thor and then reprised the role in the 2013 sequel Thor: The Dark World, as well as 2012's The Avengers and 2015's Avengers: Age of Ultron. Skarsgård reteamed with Thor director Kenneth Branagh for the 2015 film Cinderella, in which he played The Grand Duke. On 9 January 2018, it was announced that he will star as the villainous Vladimir Harkonnen in Dennis Villeneuve‘s upcoming Duneadaptation.

Skarsgård has also appeared in music videos alongside fellow Swedes. He was in Eva Dahlgren's "Vem Tänder stjärnorna" (Who Lights the Stars) in 2009 and Lykke Li's 2011 music video, "Sadness Is a Blessing".