[3] On screen, he made his film debut in Sidney Lumet's Fail Safe (1964), and appeared in Marathon Man (1976), Black Sunday (1977), Demon Seed (also 1977), Creepshow (1982), and The Thomas Crown Affair (1999).

Weaver portrayed Dr. Josef Weiss in the 1978 television miniseries Holocaust, for which he was nominated for a Primetime Emmy Award for Outstanding Lead Actor in a Limited Series or Movie.

[4] He was also a fixture as a featured and guest actor on science fiction and fantasy shows, including The Twilight Zone, 'Way Out, Night Gallery, The Martian Chronicles, Star Trek: Deep Space Nine, and The X-Files.

His other Broadway credits included The Chalk Garden (Tony nomination and Theatre World Award win), All American, Baker Street, Absurd Person Singular, “The Price,” Love Letters, and The Crucible.

He appeared in such movies as Fail-Safe (1964; as a jingoist and increasingly unstable U.S. Air Force colonel, ashamed of his foreign-born and alcoholic parents, whom he refers to as "those people"), Marathon Man (1976; as a professor advising the protagonist, a graduate student), Black Sunday (1977; as the lead FBI agent in an anti-terrorism effort), Creepshow (1982; as a scientist who discovers a monster in a crate), and John McTiernan's remake of The Thomas Crown Affair (1999).

[10] Shortly thereafter, he came out of retirement to make an uncredited cameo in This Must Be the Place (2011), voicing the deceased father of Sean Penn's protagonist.

He went on to give prominent supporting performances in the Emmy-nominated television film Muhammad Ali's Greatest Fight (2013) and the theatrically released We'll Never Have Paris (2014), The Cobbler (2014), and The Congressman (2016).