The last filmed episode of The Lucy-Desi Comedy Hour: Lucy Meets the Mustache (1960) was the last time Lucille Ball and Desi Arnaz would work together. Immediately after filming, Lucille Ball filed for divorce. This episode - and the background drama of these 2 - had been subsequently talked about. (Edie Adams discussed in detail that during the filming - and especially whilst she was singing, Lucy's eyes were visibly red... from crying. Though Ms Adams says no one on the set discussed, or even knew exactly what was going on).

Near the end of the series, William Frawley and Vivian Vance were offered their own spin-off series. William Frawley was for it, but not Vivian Vance; neither got along well with another, off-camera. Vance turned it down primarily due to not wishing to continue to work with Frawley. She also felt the Mertzes as leads would not work without the Lucy (Lucille Ball) character.

A major plotline of the final episodes of I Love Lucy (1951) (and the reason the Mertzes were able to move to Connecticut) was running the egg farm on the Ricardo's property.,During the entire run of The Lucy-Desi Comedy Hour (1957), the egg business plot was dropped, except a single mention in one episode

When this series was still being negotiated by Desi Arnaz, with CBS, a big sticking problem in negotiations was... money (what else is new?). I Love Lucy (1951)'s sponsors (P&G and General Foods) would pull out, due to the cost, and limited number of episodes (meaning less ad time but at a higher cost). Ford Motors agreed - to promote their brand new car (the Edsel). They pulled out before the second series of episodes. Westinghouse became sponsor for the next 2 seasons, with a contract for 7 episodes (8 were produced).

The Ricardo's Connecticut neighbors, the Ramsey's, (Ralph, Betty and son, Bruce), appear in 8 of the final I Love Lucy (1951) episodes. Lucy developed a relationship with Betty Ramsey (sometimes to Ethel's annoyance, During The Lucy-Desi Comedy Hour (1957), the Ramsey family was dropped, their name only mentioned twice; as little Ricky's babysitters.

The Lucy-Desi Comedy Hour (1957) never had a formal finale (which was a rare thing in those early years, anyway). Plans had been made early in 1960 for another (1961) series of episodes, and Debbie Reynolds had been signed to appear in one. No other signings were made. The regular cast were subsequently released in April, 1960, with the series' cancellation.

Little Ricky actor, Richard Keith was in all but one of this series' episodes. The only The Lucy-Desi Comedy Hour (1957) episode without him was the 8th; The Lucy-Desi Comedy Hour: Lucy Goes to Alaska (1959).

The series was introduced each week by Marvin Miller (uncredited).

The reason of the series' name change (from I Love Lucy (1951)) was that shows' title - along with all the first several years worth of episodes - had been sold to CBS. The sale was done to give Ball and Arnaz the money needed too complete their purchase of RKO Studios, subsequently known as Desilu Studios (subsequently purchased in the late 1960's by Gulf+Western).

Hazel Pierce, who was Lucy's stand-in, appears in three episodes. Pierce also makes appearances in Lucy's other series.