Gentleman detective Philo Vance (Paul Lukas) begins an investigation when he receives an anonymous letter stating that society man Lynn Llewellyn (Donald Cook) will be in danger when he appears at the casino owned by his uncle, Kinkaid (Arthur Byron). Vance visits the Llewellyn estate, which is run by Mrs. Priscilla Kinkaid-Llewellyn (Alison Skipworth), the matriarch of the household, and stumbles into one of the family's many quarrels. At the end of the bitter quarrel, which involves Mrs. Llewellyn's son Lynn and his wife Virginia (Louise Henry), Virginia announces that she has decided to leave the house and go to Chicago. During the tiff, Vance and Doris (Rosalind Russell), Mrs. Llewellyn's secretary, are introduced to each other and Doris immediately takes a liking to Vance.
Vance takes Doris to his home, where he and District Attorney Markham (Purnell Pratt) show her the mysterious letter. Doris immediately recognizes the return address as being that of the Llewellyn's townhouse in Closter and notices that the letter was typed on her typewriter. Vance assigns Sergeant Heath (Ted Healy) to help stake out the casino that night, but their presence does not prevent Lynn from suddenly collapsing at the card table. At the same time, Doris informs Vance that Virginia has died at the Llewellyn house. Markham begins his investigation of the murder by questioning Mrs. Llewellyn, who recalls having quarrelled with Virginia before she was poisoned, and Amelia (Isabel Jewell), Mrs. Llewellyn's daughter, who admits that she too had a spat with Virginia. Meanwhile, Doris finds Mrs. Llewellyn's recently altered will, in which she disinherited Kinkaid, making it apparent that Lynn and Amelia would be the only ones who would benefit from Mrs. Llewellyn's death.
Other clues begin to surface, including Kinkaid's unusual collection of books on chemistry and poisons, and a loaded gun found in Virginia's bedroom. Soon after Lynn's recovery, Mrs. Llewellyn is found dead of an apparent suicide with a note, bearing her signature, in which she confesses to Virginia's murder. Not convinced that the mystery has been solved, Vance pursues his theory that Mrs. Llewellyn may have been poisoned by heavy water, which leads him to Kinkaid's secret laboratory, where he and Doris are captured and held at gunpoint by Kinkaid. Vance and Doris escape, but Vance does not believe that Kinkaid is the murderer, thinking instead that he is merely one of many decoys set up by the real killer to lead the investigation astray.
The real killer turns out to be Lynn, who has lured Vance and Doris to the Closter townhouse to kill them. But before Lynn completes his "perfect crime," Vance reads from a letter he wrote earlier in which he detailed his theory about the killings. In it, Vance names Lynn as the murderer, calling him a rich, ego-maniacal weakling, who, being tired of his wife, poisoned her and threw the blame on his uncle, whom he despised. After hearing Vance's summary of the murder plot, Lynn tells his captors that he has arranged to pin Vance and Doris' forthcoming murder on Kinkaid. However, when Lynn shoots Vance, Heath and others emerge from behind a door where they have been recording Lynn's confession and arrest him. After thanking Becky, Mrs. Llewellyn's maid (Louise Fazenda), for loading Lynn's gun with blanks, Vance resumes his romance with Doris.
Cast notes:Rosalind Russell considered both the film and her performance in it to be "so bad". She wrote in her autobiography, Life is a Banquet, that MGM forced the role on her, and that afterwards her maid would tell her "If you don't behave ... I'm going to tell people about that Casino Murder Case."
Originally William Powell and Myrna Loy were intended to star in The Casino Murder Case, but Powell was tired of playing Vance – he was the first actor to play the part on film, and had played in the part in five earlier films – so MGM planned to use Otto Kruger, and then Fred Keating (who would have been borrowed from Columbia Pictures), Warren William and Ricardo Cortez, before settling on Paul Lukas. Eugene Pallette was to have played the police sergeant, but was first replaced by Edward Brophy and then Ted Healey. Constance Collier was to have played "Mrs. Llewellyn" before Alison Skipworth was borrowed from Paramount Pictures for the role.
Andre Sennwald in the New York Times wrote, "Paul Lukas just isn't the Philo Vance type and his reticent drawing-room manner seems a feeble substitute for the dashing qualities which made William Powell the best of the cinema Philos. Rosalind Russell works very hard at being agreeable in the Myrna Loy style, but with no vast success. Miss Skipworth, of course, is characteristically excellent as the foolish dowager, and there are good performances by Arthur Byron as the chief suspect and the comical Ted Healy as the halfwit detective. The best work in the film, though, is contributed by Isabel Jewell as the morbid and dipsomaniac daughter of the house."
More recently, Turner Classic Movies called the film "a diverting series entry that was faithful to Van Dine's original story," while Allmovie agreed that Paul Lukas "is simply not the right type for the part" and that "it is largely because of Lukas that the film is not one of the better entries in the series." The review characterizes the work of Alison Skipworth and Isabel Jewell as "excellent" and Eric Blore and Charles Sellon as "strong" performances, but says that Rosalind Russell "hasn't quite yet hit her stride here." As a result, the mix of comedy and mystery in the film "isn't as smooth as one might wish."