Just as Bob Hope's My Favorite Blonde (1942) was a takeoff on Alfred Hitchcock, Hope's My Favorite Brunette was a lampoon of the noirish hard-boiled detective school popularized by Raymond Chandler. Awaiting execution on death row, Hope tells the gathered reporters how he got into his present predicament.
It seems that Hope was once a baby photographer, his office adjacent to the one leased by a private detective (played in an amusing unbilled cameo by Alan Ladd). While hanging around the p.i.'s office, Hope is mistaken for the detective by beautiful client Dorothy Lamour.
She hires Hope to search for her missing uncle, and also entrusts him with a valuable map. Hope's diligent (if inept) sleuthing takes him to a shady rest sanitarium, where he runs afoul of lamebrained henchman Lon Chaney, Jr. and sinister, knife-throwing Peter Lorre.
Both are in the employ of attorney Charles Dingle, who is responsible for the disappearance of Lamour's uncle. Escaping the sanitarium with Lamour in tow, Hope follows the trail of evidence to noted geologist Reginald Denny. The geologist is murdered, and Hope is accused of the crime.