After recovering from tetrodotoxin poisoning at the hands of SMERSH agent Rosa Klebb, MI6 agent James Bond is sent by his superior officer, "M", on a rest cure trip to Jamaica. Once on the island his task is a simple investigative assignment looking into the disappearance of Commander John Strangeways, head of the MI6 station J in Jamaica, and his missing secretary.
Bond is briefed about Strangeways who had been investigating the activities of Dr Julius No, a reclusive Chinese-German man who lives on Crab Key and operates a guano mine. The island has a colony of roseate spoonbills at one end and is said to be the home of a vicious dragon. The spoonbills are protected by the National Audobon Society, two representatives of which had died when their aircraft crashed on Dr No's airstrip. On his arrival in Jamaica, Bond realizes he is being watched, as his hotel room has been searched, a basket of poisoned fruit supposedly a gift from the colonial government, is delivered to his room, and a deadly centipede is placed in his bed whilst he is sleeping.
Enlisting the help of his old friend, Quarrel, Bond visits Crab Key to find out if there is a connection between Dr No and Strangeways' disappearance. Whilst on Crab Key the men meet Honeychile Rider who visits the usland to collect valuable shells. Bond and Honey are captured by Dr No's men after Quarrel is burned to death by the doctor's "dragon" - a flame-throwing, armored swamp buggy that Dr No uses to deter trespassers.
Bond discovers that Dr No is also working with the Russians and has constructed an elaborate underground facility from which he can sabotage American missile tests at nearby Cape Canaveral.Dr No had previously been a member of a Chinese Tong, but he was captured by the organization after he stole a lot of money from their treasury, a crime punishable by the cutting off of his hands. The Tong leaders also ordered him shot. They believed they had shot him through the heart, but were unaware of his dextrocardia, a condition that means his heart is on the right side of his body. The bullet cobsequentky missed his heart and he survived. Interested in the ability of the human body to absorb and withstand pain, Dr No forces Bond to navigate his way through a sadistic obstacle course constructed in the facility's ventilation system. He is kept under regular observation and suffers electric shocks, burns and an encounter with large poisonous spiders as he negotiates the course. The ordeal ends with a fight against a captive giant squid which Bond defeats using improvised stolen objects that he has made into weapons. After his escape he encounters Honey who had been pegged out to be eaten by crabs; however the crabs ignored her and she was able to make her own bid to escape.
Bond kills Dr No by taking over the guano-loading machine at the docks and diverting the flow of guano from it to bury the villainous doctor alive. Bond and Honey then escape from Dr No's complex in the dragon buggy.