Cnidus was founded by Dorian Greeks from the Peloponnese, probably from Lacedaemon or Argos, in the centuries after the fall of the Mycenaean palaces. The colonists settled on the Datca Peninsula, a rugged spit of land that divides the Aegean Sea from the Gulf of Doris, and they built their city on the very tip of the peninsula, where the two seas meet. The site was chosen for its harbours. Cnidus had not one but two natural harbours, one on the Aegean side and one on the Mediterranean, making it a perfect entrepot for trade between the Greek world and the East. The city became a member of the Dorian Hexapolis, the league of six Dorian cities that included Halicarnassus and Cos, and it was famous for its wine, its wool, and its medical school.

The mythic significance of Cnidus lay in its connection to Aphrodite. While the island of Cyprus was universally recognised as the goddess's birthplace, some traditions claimed that she had first stepped onto land at Cnidus, rising from the foam of the sea at the very tip of the peninsula. The Cnidians built a magnificent temple to her, a circular tholos that stood on a terrace overlooking the sea, and they commissioned Praxiteles, the greatest sculptor of the 4th century BCE, to create a cult statue for the sanctuary. The result was the Aphrodite of Cnidus, the first life-size nude statue of a goddess in the history of Greek art. Praxiteles had originally offered the statue to the island of Cos, but the Coans, shocked by the nudity, chose a clothed version instead. The Cnidians bought the nude Aphrodite and placed her in their temple, where she became one of the most famous works of art in the ancient world.

The statue was extraordinary. Aphrodite stood with one hand covering her groin and the other reaching for a robe draped over a water jar, caught in the moment of bathing. The marble was so finely worked that the flesh seemed to glow with life, and the expression on the goddess's face was at once modest and inviting. Pilgrims came from across the Mediterranean to see her. Pliny the Elder, the Roman writer who catalogued the wonders of the world in his Natural History, reported that a young man had fallen so desperately in love with the statue that he hid in the temple at night and tried to make love to the marble, leaving a stain on her thigh that could never be removed. The emperor Nicomedes of Bithynia offered to pay off the entire debt of Cnidus in exchange for the statue, but the Cnidians refused. They would rather, they said, lose their city than their Aphrodite.

Cnidus was also the birthplace of Ctesias, the physician and historian whose works shaped the Greek imagination of the East. Ctesias served as the royal doctor to Artaxerxes II, the Persian king who reigned from 404 to 358 BCE, and he used his position at the court of Susa to gather material for two extraordinary books. The Persica was a history of the Near East in twenty-three books, filled with court intrigue, poisonings, and sensational detail. The Indica described the wonders of India, including the manticore, the man-eating monster with a lion's body, human face, and scorpion tail, which Ctesias claimed to have seen brought to the Persian king as a gift. Whether Ctesias actually saw these creatures or simply recorded the tales of travellers, his books were enormously influential. Herodotus, the father of history, devoted a passage to Ctesias and his disappearances, and the manticore became a fixture of Greek and Roman natural history for fifteen hundred years.

The city flourished through the Hellenistic and Roman periods. It was a free city under Roman rule, and its medical school was famous throughout the empire. The astronomer Eudoxus of Cnidus, who studied under Plato in Athens, developed a system of concentric spheres to explain the movements of the planets, a model that dominated Western astronomy until the Renaissance. The physician Ctesias was not the only medical man of note; Cnidus was renowned for its empirical approach to medicine, in contrast to the more theoretical school of Cos associated with Hippocrates. Pausanias, the Greek traveller who walked through Asia Minor in the 2nd century CE, reported that the temple of Aphrodite was still standing and that the statue of Praxiteles was still venerated. But the city declined in the Byzantine period, and by the Middle Ages it was abandoned. Today, the ruins of Cnidus lie scattered across the Datca Peninsula, the circular foundation of Aphrodite's temple still visible above the sea, a reminder of the city that chose a marble goddess over its own freedom.