The picture stars Irene Dunne as a woman who, after being shipwrecked on a tropical island for several years and declared legally dead, returns to her [former] husband (Cary Grant) and children.

After seven years, lawyer Nick Arden has his wife Ellen, missing since her ship was lost, declared legally dead so he can marry Bianca.

Further complications ensue when an insurance adjuster mentions to Nick a rumor that Ellen was not alone on the island, but had the company of Stephen Burkett, and that they called each other "Adam" and "Eve".

After the great success of The Awful Truth (1937), McCarey signed Cary Grant and Irene Dunne for the film without a script.

[3]: 148  "On My Favorite Wife," recalled Gail Patrick, "we were desperately trying to be funny as our producer, Leo McCarey, lay at death's door from an automobile crash.

"[4]: 290  A number of pre-production conferences took place in the hospital, and McCarey recovered sufficiently to visit the set two or three weeks into filming.

[2]: 418–419 So the cast was dismissed, the writers went home, the director went back to New York, and I sat there with the cutter trying to figure out what to do to save the picture.

[2]: 419 Patrick later said she felt that the resolution of the film should have included a romance between her character, Bianca, and Stephen Burkett (Randolph Scott).

"[9] "Both in theme and execution, My Favorite Wife was a quasisequel to The Awful Truth," wrote RKO studio chronicler Richard B. Jewell in 1982.

"[3]: 148 In 1991, Pauline Kael assessed My Favorite Wife as "the most famous and the funniest" modern version of Tennyson's story "Enoch Arden" (1864).

[10] Bella and Sam Spewak and Leo McCarey were nominated for the Academy Award for Best Story, Roy Webb for Best Score, and Van Nest Polglase and Mark-Lee Kirk for Best Art Direction.

The March 23, 1941, broadcast of The Screen Guild Theater presented a 30-minute adaptation of the film, with Dunne reprising her role and Robert Montgomery as Nick Arden.

[13][14] Grant and Dunne also reprised their roles when the movie was adapted for the December 7, 1950, broadcast of Screen Director's Playhouse.

[12] 20th Century Fox began filming a 1962 remake starring Marilyn Monroe, Dean Martin, and Cyd Charisse under the working title of Something's Got to Give, which was to be directed by George Cukor.

In 1963, 20th Century Fox remade the film as Move Over, Darling, starring Doris Day and James Garner.