Jeroen Krabbé's first big American film was the Whoopi Goldberg comedy Jumpin' Jack Flash. However, it is was role as villain in a string of international films from the late 1980's and early 1990's which brought him international stardom, with notable roles such as Losado in No Mercy (1986), General Georgi Koskov in the James Bond film The Living Daylights (1987), Gianni Franco in The Punisher (1989), Herbert Woodruff (Lowenstein's husband) in The Prince of Tides (1991), and Dr. Charles Nichols in The Fugitive (1993). He has also appeared in numerous TV productions, and as Satan in the TV production Jesus.

He has been both director and producer of a 1998 film about Orthodox Jews during the 1970s in Antwerp (Flanders) co-starring Isabella Rossellini and Maximilian Schell called Left Luggage, as well as the Harry Mulisch novel adapted into film The Discovery of Heaven. Left Luggage was entered into the 48th Berlin International Film Festival. The following year, he was a member of the jury at the 49th Berlin International Film Festival.

His television work includes playing an uncanny psychic in series 11 of Midsomer Murders, "Talking to the Dead." Apart from acting and directing he is an accomplished artist (his paintings have graced Dutch postage stamps) and co-authored a Dutch cookbook. In November 2004 he released the book Schilder, which is an overview of his paintings.

Krabbé has three sons, Martijn, Jasper and Jacob. His brother is master chess player, journalist, and novelist Tim Krabbé.