Von Sydow was first noticed internationally for playing the 14th-century knight Antonius Block in Ingmar Bergman's The Seventh Seal (1957), which features iconic scenes of his character challenging Death to a game of chess.

He appeared in eleven films directed by Bergman, including Wild Strawberries (1957), The Virgin Spring (1960), Through a Glass Darkly (1961), Winter Light (1963), Shame (1968), and The Touch (1971).

[6] Originally expected to pursue a career in law, he became interested in acting after seeing a production of A Midsummer Night's Dream during a class trip to Malmö,[14][15] which prompted him to establish an amateur theatrical group along with his friends back at school.

[16] He made his stage debut in a small part in the Goethe play Egmont, which he considered "almost a disaster," but received good reviews for his performance.

[17] Sydow's theatrical work won him critical recognition, and in 1954 he received the Royal Foundation of Sweden's Cultural Award, a grant to young, promising actors.

[17] Sydow had previously sought to play a small part in Bergman's Prison (Fängelse, 1949), but the director rejected the proposition.

[19] During this period, he also had roles in films including Wild Strawberries (Smultronstället, 1957), Brink of Life (Nära livet, 1958) and Winter Light (Nattvardsgästerna, 1963).

In his company were Gunnar Björnstrand, Ingrid Thulin, Bibi Andersson and Gunnel Lindblom, all frequent collaborators of Bergman on screen.

[22] In 1965, Sydow finally accepted George Stevens's offer and made his international debut, playing Christ in the epic The Greatest Story Ever Told.

[19] He accepted the part against the advice of Bergman, spent six months at the University of California, Los Angeles, preparing for the role, and adopted a Mid-Atlantic accent.

[10] To his own frustration, however, Sydow would become frequently cast in villainous roles, such as a neo-Nazi aristocrat in The Quiller Memorandum (1966), a Russian colonel in The Kremlin Letter (1970), a meticulous and elegant international assassin in Three Days of the Condor (1975), Emperor Ming the Merciless in Flash Gordon (1980) and James Bond's nemesis Ernst Stavro Blofeld in Never Say Never Again (1983).

[17] In 1977, Sydow made his Broadway debut alongside Eileen Atkins and Bibi Andersson in Per Olov Enquist's The Night of the Tribades, a play about the writer August Strindberg.

[6] Sydow made his British stage debut at The Old Vic in 1988 as Prospero in The Tempest, a role he had first played in Sweden three decades before.

[15][24] In the 1980s, in addition to Flash Gordon and Never Say Never Again, Sydow appeared in John Milius's Conan the Barbarian (1982), Jan Troell's Flight of the Eagle (1982), Rick Moranis's & Dave Thomas's Strange Brew (1983), David Lynch's Dune (1984) and Woody Allen's Hannah and Her Sisters (1986).

[25] In the 1987 Bille August film Pelle the Conqueror, Sydow portrayed an impoverished Swedish labourer who brought his son to Denmark to try to build a better life for themselves.

[26] In 1989, Sydow appeared in the television film Red King, White Knight, for which he received his first Primetime Emmy Award nomination.

[6] Throughout the rest of the 1990s, Sydow also appeared in films such as Father (1990), Awakenings (1990), Until the End of the World (1991), Needful Things (1993), Judge Dredd (1995) and Snow Falling on Cedars (1999).

[27] In 2002, Sydow acted in one of his biggest commercial successes, playing the PreCrime director opposite Tom Cruise in Steven Spielberg's science fiction thriller Minority Report.

[17] In 2007, he starred in the box-office hit Rush Hour 3 as one of the antagonists opposite Jackie Chan and Chris Tucker, and played the father of the protagonist in The Diving Bell and the Butterfly, Julian Schnabel's adaptation of the memoir by Jean-Dominique Bauby.

[17] He received his second Academy Award nomination for his performance as a mute elderly renter in Stephen Daldry's Extremely Loud & Incredibly Close (2011), based on the novel by Jonathan Safran Foer.

He portrayed Nicolas Andreou, one of the last living survivors of the Kalavryta massacre of 1943 committed by Nazi troops during the Axis occupation of Greece.

[16] He was nominated for two Academy Awards, for his performances in Bille August's Pelle the Conqueror (1987) and Stephen Daldry's Extremely Loud & Incredibly Close (2011).