The sixth novel in Ian Fleming's James Bond series opens in Kingston, Jamaica, where Commander John Strangways, the British Secret Service's Regional Control Officer for the Caribbean, leaves his evening bridge game at Queen's Club to make a scheduled radio contact with London. Three assassins disguised as blind beggars ambush him on the sidewalk and shoot him with silenced revolvers. At his bungalow, his second-in-command, Mary Trueblood, is killed at the radio transmitter. The killers destroy the cipher books, burn the bungalow, and sink both bodies in a weighted coffin in the Mona Reservoir, erasing all trace of the Caribbean station.
Three weeks later in London, M, the head of the Secret Service, summons James Bond, one of his top agents, to investigate. Bond has been convalescing after being poisoned with fugu, a lethal fish toxin, on his last mission. M forces Bond to surrender his Beretta .25 pistol, which jammed during his last assignment, and accept replacements: a Walther PPK 7.65mm and a Smith & Wesson Centennial Airweight .38 revolver.
M presents the disappearance as a probable elopement, but the Chief of Staff, Bond's closest friend at headquarters, disagrees: Strangways left his bridge game promising to return in twenty minutes, and the final radio contact broke off abruptly. Bond sides with the Chief of Staff, insisting Strangways would never have abandoned the Service. He asks about Strangways's last case and learns of a complaint from the Audubon Society concerning their roseate spoonbill sanctuary on Crab Key, a small island between Jamaica and Cuba owned by Doctor Julius No. Doctor No is a half-Chinese, half-German recluse who purchased the island in 1943 to mine guano, a valuable fertilizer derived from bird dung. Two Audubon wardens died under suspicious circumstances, one allegedly killed by a fire-breathing "dragon," and two investigators died in a plane crash on the island's airstrip. M dismisses the situation as trivial, but Bond takes the file, noting that at least four people have died and perhaps Strangways and Trueblood make six. Bond senses M is punishing him with a soft assignment and leaves headquarters angry.
In Kingston, Bond is met by Quarrel, a Cayman Islander and ally from a previous mission. A Chinese photographer takes Bond's picture at the airport, and a taxi follows them, confirming organized surveillance. Bond dispatches Quarrel to rent a new car, hire decoys to drive a false trail, and secure a hidden base at a bungalow called Beau Desert. The Colonial Secretary, Pleydell-Smith, briefs Bond on Doctor No's guano operation, estimating the birds and installations on Crab Key are worth roughly two and a half million dollars. When Pleydell-Smith requests the Crab Key files, his secretary, Miss Taro, a Chinese woman, reports the contents missing. Bond deduces she is Doctor No's agent inside King's House, the seat of the Jamaican government, noting that an old dossier on Bond conveniently appeared on her desk.
Two assassination attempts follow in rapid succession. A fruit basket at Bond's hotel contains cyanide injected through pinholes, and that night a large centipede planted in his room crawls up his body while he lies frozen before he kills it. The two decoys driving the false trail are killed in a staged car crash.
After a week of physical training, Bond and Quarrel prepare for a covert reconnaissance of Crab Key. Bond arranges life insurance for Quarrel, who has a premonition of his own death but follows without hesitation. They sail thirty miles by canoe and land on the island's south shore before dawn. The next morning, Bond discovers Honeychile Rider, known as Honey, collecting rare shells on the beach. Honey is a Jamaican orphan who lives alone in the cellars of a ruined plantation house, educated from a salvaged encyclopedia. Her nose was broken during a sexual assault by an overseer when she was fifteen, and she sells shells to save for corrective surgery. She has seen the "dragon" on previous visits, which Bond suspects is a disguised vehicle.
Honey sails to the island with her sail raised, alerting Doctor No's radar. A patrol boat rakes the coastline with machine-gun fire, destroying Honey's canoe and stranding the trio. They trek upriver through mangrove swamps, evading a search party with Dobermann pinschers by submerging and breathing through bamboo tubes. That evening, Honey tells Bond her story: Orphaned at five and raised by a devoted nanny, she took revenge on the overseer by placing a Black Widow spider on his sleeping body. She makes Bond promise he owes her "slave-time." Bond privately resolves to fund her surgery.
That night, the "dragon" crosses the lake toward them: an armored marsh buggy with a diesel engine, headlamp "eyes," and a flame-thrower mounted in a mock dragon's snout. Bond and Quarrel open fire, but bullets bounce off the armor. The flame-thrower incinerates Quarrel instantly. A loudspeaker orders surrender. Bond goes to Quarrel's charred remains, whispers an apology, and covers the remains of his eyes with sand before surrendering with Honey.
Inside Doctor No's mountain fortress, surreal luxury masks their captivity: carpeted corridors, a bedroom suite with no windows or door handles, and drugged food. While they sleep, Doctor No enters and examines their bodies using his steel pincers. They are brought before him in his underwater study, where one wall of armored glass looks into the sea. Doctor No is at least six foot six, bald, with steel pincers for hands. Born in Peking, he rose through the Shanghai Tongs, a network of Chinese criminal organizations, and became treasurer of the Hip Sings Tong in New York. He stole a million dollars in gold, was caught, had his hands cut off, and was shot through the heart, surviving because his heart sits on the right side of his body. He found Crab Key, spent fourteen years building his fortress, and destroyed the bird sanctuary, killing wardens, investigators, Strangways, and Trueblood to protect his operations.
Doctor No reveals his true purpose: Russian-trained technicians and radio equipment capable of interfering with American guided missile tests launched from Turks Island. He plans to escalate to capturing prototype missiles or redirecting rockets into cities. He sentences Honey to be staked out on the mountainside in the path of migrating land crabs and subjects Bond to a lethal obstacle course through the mountain's ventilation shafts.
Bond endures electrified grilles, a vertical climbing shaft, superheated metal that burns through his improvised wrappings, and a cage of giant tarantulas before being ejected from a chute into the sea. He fights off a giant squid in a deep-water inlet, then follows a rocky track to the guano-loading jetty, where Doctor No supervises a crane pouring guano into a tanker's hold. Bond kills the crane operator, takes the controls, and swings the conveyor's spout at Doctor No, burying him alive under tons of guano.
In the conveyor tunnel, Bond finds Honey alive. The crabs ignore her still body, and she frees herself and enters the tunnel intending to kill Doctor No. Bond shoots three guards, and they commandeer the marsh buggy, driving to the coast and sailing back to Jamaica in Quarrel's canoe.
In Kingston, the authorities agree to send a warship to Crab Key. Bond signals M, closing with a sardonic note about the ineffectiveness of his Smith & Wesson against a flame-thrower. He arranges Honey's nose operation in New York at his expense and secures her a position at the Jamaica Institute. Back at Beau Desert, Honey has left a note claiming her "slave-time." She leads Bond to her home in the cellars of the ruined Great House: an elegant room of polished cedar lit by a silver chandelier and set with old family silver. Over a candlelit dinner, they surrender to their mutual attraction.