Prescription: Murder is the first ever episode of Columbo. It first aired on February 20, 1968 and was directed by Richard Irving. The episode stars Peter Falk in his first appearance as Columbo and Gene Barry as the series' first murderer, Dr. Ray Fleming. Another pilot was made in 1971, Ransom for a Dead Man, before the series began officially with Murder by the Book later that same year.
Dr. Ray Fleming (Gene Barry), a psychiatrist, murders his wife (Nina Foch) and persuades his mistress Joan Hudson (Katherine Justice), who is an actress and one of his patients, to support his alibi by impersonating her. Final clue/twist: Columbo stages the suicide of Fleming’s mistress, then urges him to confess now that the love of his life has killed herself for him. Fleming mocks Columbo’s words, saying he never cared deeply for Joan and would have gotten rid of her eventually anyway. Joan, listening in, agrees to testify against Fleming.