John Strangways, the MI6 Station Chief in Jamaica, meets a grim fate when he is murdered along with his secretary by a trio of assassins, informally dubbed The Three Blind Mice. Their mission culminates in a burglary of his residence, where critical files regarding Crab Key Island and the elusive Dr. No are stolen. Concerned about Strangways’s mysterious disappearance, M, the head of MI6 portrayed by Bernard Lee, assigns agent James Bond, played by Sean Connery, to investigate the incident. This assignment also involves determining whether Strangways's cooperation with the CIA, regarding a case about disrupted rocket launches due to radio jamming, is intertwined with his murder.
Meanwhile, Bond is introduced to Miss Moneypenny, M's dedicated secretary, as well as Major Boothroyd, who replaces Bond's regular firearm, the Beretta M1934, with a Walther PPK for increased safety and effectiveness.
Upon arriving in Jamaica, Bond encounters a man posing as a chauffeur, who is, in fact, an enemy agent attempting to eliminate him. However, the agent ends up taking his own life with a cyanide capsule disguised as a cigarette before Bond can extract any information. Following this, Bond investigates Strangways's residence, where he meets a boatman named Quarrel, who enables him to make contact with CIA's agent Felix Leiter. These developments lead Bond to uncover that Strangways was close to pinpointing the source of a radio jamming signal traced back to Jamaica. Quarrel reveals that they previously gathered mineral samples from Crab Key, an island owned by Dr. No, who is known for his bauxite mine and strict regulations against visitors.
Investigating further, Bond finds a receipt from Professor R.J. Dent, a geologist who secretly works for Dr. No and raises suspicions regarding the authenticity of his findings on Stratngways's samples. Informed of Bond’s inquiries, Dent rushes to Crab Key to relay the information to his employer. Following orders, Dent attempts to assassinate Bond using a tarantula, but Bond manages to survive the attack.
Additionally, Bond encounters Miss Taro, a secretary with dubious loyalties who is revealed to be a double agent working for Dr. No. Their meeting culminates in an invitation to her cabin, but, during this encounter, Bond successfully thwarts yet another attack by the Three Blind Mice. After overhearing a suspicious call from Taro confirming Bond’s presence to an unknown party, he apprehends her and discovers that Dent is involved.
As the investigation deepens, Bond discovers that Strangways may have suspected the radio jamming emanated from Crab Key, prompting him to coerce Quarrel into sailing to the island. Once they arrive, Bond meets Honey Ryder, a determined shell diver portrayed by Ursula Andress, who suspects foul play in her father’s disappearance linked to his research on the island.
The trio faces an ambush by armed henchmen, leading to Quarrel’s tragic demise. Subsequently, Bond and Ryder are captured and taken to a concealed base where they undergo a decontamination procedure due to radiation exposure from the swamp. After being subdued, they find themselves at a dinner with Dr. No, a complex antagonist who reveals his motivations and plans to disrupt the Project Mercury launch at Cape Canaveral using a powerful radio beam. Dr. No, a former criminal scientist with ties to SPECTRE, proposes joining forces with Bond, to which Bond adamantly refuses.
In retaliation, Dr. No confines Ryder and Bond separately, yet Bond demonstrates his resourcefulness by escaping his cell through an air vent and disguising himself as a staff member to maneuver into the base’s control center. There, he discovers the imminent nuclear reactor powering the radio beam and seeks to sabotage it during the rocket launch.
As chaos ensues, Dr. No’s plan backfires, resulting in his demise as he falls into the reactor. With destruction imminent, Bond liberates Ryder, and together they make their escape by boat, just as the base detonate behind them. Eventually, Felix Leiter locates them adrift at sea and facilitates their rescue by a Royal Navy vessel. However, amidst the celebratory moment, Bond chooses romance over safety, cutting the tow rope to embrace Ryder passionately, signaling a bittersweet end to their harrowing adventure.
