After completing his training as an actor, Isaacs almost immediately began appearing on the stage and on television; his film debut was in a minor role as a doctor in Mel Smith's The Tall Guy (1989). He was initially known as a TV actor in the UK, with starring roles in the ITV drama Capital City (1989) and the BBC drama Civvies (1992) and guest roles in series such as Taggart and Inspector Morse in 1992. He also played Michael Ryan in ITV1's adaptation of Martina Cole's novel Dangerous Lady, directed by Jack Woods and produced by Lavinia Warner, in 1995.

On stage he portrayed the "emotionally waffling" gay Jewish lawyer Louis Ironson in Tony Kushner's Pulitzer Prize-winning Angels in America: A Gay Fantasia on National Themes, at the Royal National Theatre, in its London première, performing the role in both parts, Part One: Millennium Approaches, in 1992, and Part Two: Perestroika, in 1993. When auditioning for that role, he told the producers, "Look, I play all these toug