The part of Oscar's (Jack Klugman) ex-wife Blanche was played by Brett Somers, Klugman's own wife. The real-life couple were separated during the run of the show.
Early episodes from the first season were titled "Neil Simon's The Odd Couple". Neil Simon objected to this, having nothing to do with the television series and not wanting to leave the impression left that he did, not knowing the quality of the series' scripts (he did continue to receive a "Based on the Play created by" credit). After seeing the first two seasons of the show he became a fan of the series, and even agreed to appear as himself in a cameo in one episode.
After the show was canceled, Tony Randall won an Emmy for playing Felix Unger. As he accepted his award, he said he wished he "had a job".
The show's Nielsen ratings were low at first and it was near cancellation. High ratings for the reruns during the summer months, however, helped get the series renewed.
The original voices of Linus and Lucy from the "Peanuts" animated programs both appeared in early episodes of the series. Christopher Shea (Linus) appeared in some episodes as the across-the-hall neighbor Phillip, and Pamelyn Ferdin (Lucy) originated the role of Felix's daughter Edna.