Op Jamaica worden twee geheimagenten van de British Secret Service bruut vermoord. De baas van de geheime dienst M (Bernard Lee) geeft James Bond, speciaal agent 007 (Sean Connery) opdracht een en ander te onderzoeken. Bond komt de mysterieuze Dr. No (Joseph Wiseman), een lid van terreur organisatie S.P.E.C.T.R.E. (wat staat voor SPecial Executive for Counter-intelligence, Terrorism, Revenge and Extortion), op het spoor. Deze geniale wetenschapper wil het Amerikaanse ruimtevaartprogramma vernietigen. Bond zoekt bij zijn onderzoek de samenwerking met CIA agent Felix Leiter (Jack Lord). Hij reist af naar het mysterieuze Crab Key eiland van Dr. No. Daar ontmoet hij de bloedmooie Honey Ryder (Ursula Andress).
When the British agent John Strangways and his secretary vanish in Jamaica, James Bond is assigned by M to investigate what might have happened with the agents. 007 teams-up with the CIA agent Felix Leiter and the native Quarrel that works with him and 007 learns that Strangways was investigating the Crab Key Island that belongs to the mysterious Dr. No and is very well protected by armed guards. Soon they learn that Dr. is toppling the rockets launched by the NASA Cape Canaveral and 007 goes to Crab Key with Quarrel to seek evidences against Dr. No. They meet the sexy Honey Ryder collecting seashells in the island. They stay together but soon they are found by the security guards and arrested in Dr. No's facility, and James Bond learns the evil plan of Dr. No and The SPECTRE.
When Strangways, the British SIS Station Chief in Jamaica goes missing, MI6 send James Bond - Agent 007 to investigate. His investigation leads him to the mysterious Crab Key; the secret base of Dr No who he suspects is trying to sabotage the American space program using a radio beam. With the assistance of local fisherman Quarrel, who had been helping Strangways, Bond sneaks onto Crab Key where he meets the beautiful Honey Ryder. Can the three of them defeat an army of henchmen and a "fire breathing dragon" in order to stop Dr No, save the space program and get revenge for Strangways? Dr. No is the first film of legendary James Bond series starring Sean Connery in the role of Fleming's British super agent.