Fred Melamed was born in New York City to unmarried parents, an American actress and a British psychoanalyst. He was adopted as an infant by Manhattanites Lou and Syma Melamed, who were involved in the television industry, with his adoptive father producing shows such as Car 54, Where Are You?, Sergeant Bilko, and Let's Pretend.
Melamed received his theatrical training at Hampshire College and the Yale School of Drama, where he was influenced by renowned artists such as James Earl Jones, John Madden, Athol Fugard, and George Roy Hill. He was a company member of the Guthrie Theater in Minneapolis and performed at The Kennedy Center, The Yale Repertory Theater, and New York's West Bank Cafe. He made his Broadway debut in the Tony Award-winning Amadeus in 1983.
Melamed has had a prolific career in television, starring in shows such as WandaVision, Medical Police, The Morning Show, Lady Dynamite, Casual, Fargo, Girls, Brooklyn Nine-Nine, New Girl, The Good Wife, and Adventure Time. He has also appeared in numerous films, including Woody Allen's Hannah and Her Sisters, Another Woman, Crimes and Misdemeanors, Radio Days, Husbands & Wives, Hollywood Ending, and Shadows and Fog. His most notable film role was as the villainous Sy Ableman in Joel and Ethan Coen's A Serious Man, which earned him an Independent Spirit Robert Altman Award and recognition from several prominent critics.
Melamed has also worked as a writer, producing screenplays such as Girl of the Perfume River, A Jones for Gash, and The Preservationist, a television series inspired by the case of his college friend, Edward Forbes Smiley III, a renowned cartographic expert and dealer who was convicted of stealing maps.
In his personal life, Melamed lives with his wife, Leslee, and twin sons in Los Angeles. Both of his children were born with autism, and he and his wife have been involved in advocacy for individuals with autism spectrum disorder and their families.