Murder, My Sweet is considered one of the better adaptations of Chandler. Glenn Erickson wrote, "Murder, My Sweet remains the purest version of Chandler on film, even if it all seems far too familiar now."
Alison Dalzell, writing for the Edinburgh University Film Society, notes:
Of all the adaptations of Chandler novels, this film comes as close as any to matching their stylish first person narrative and has the cinematic skill and bravado of direction to carry it off. Since the '40s countless mystery and neo-noir films have been made in Hollywood and around the world. Murder, My Sweet is what they all aspire to be.
According to film critics Ellen Keneshea and Carl Macek, the picture takes Chandler's novel and transforms it into a "film with a dark ambiance unknown at [the] time". Dymytryk was able to transcend the tough dialogue and mystery film conventions by creating a "cynical vision of society". As such, the film enters the world of film noir.
When the film was released, Bosley Crowther, the film critic for The New York Times, appreciated the adaptation of Chandler's novel and lauded the acting and writing:
Practically all of the supporting roles are exceptionally well played, particularly by Mike Mazurki, the former wrestler, as the brutish Moose Malloy; Otto Kruger as Jules Amthor, quack-psychologist and insidious blackmailer; Anne Shirley as an innocent among the wolf pack, and Don Douglas as the police lieutenant. In short, Murder, My Sweet is pulse-quickening entertainment.
The staff at Variety magazine also gave the film kudos, writing:
Murder, My Sweet, a taut thriller about a private detective enmeshed with a gang of blackmailers, is as smart as it is gripping ... Performances are on a par with the production. Dick Powell is a surprise as the hard-boiled copper. The portrayal is potent and convincing. Claire Trevor is as dramatic as the predatory femme, with Anne Shirley in sharp contrast as the soft kid caught in the crossfire.
The film made a profit of $597,000.