Belon was born in Le Mans, France, and studied medicine in Paris. In 1540 he went to Germany to study botany, becoming a leading figure in the 16th-century revival of natural history that followed the great voyages, the invention of printing, and the new artistic realism of the Renaissance.

Between 1546 and 1549 Belon traveled in the eastern Mediterranean countries, comparing the animals and plants he observed with their descriptions by classical authors. The results were published as Les Observations des plusieurs singularitez et choses mémorables trouvées en Grèce, Asie, Judée, Egypte, Arabie et autre pays éstranges (1553; Observations of Many Singularities and Memorable Items in Greece, Asia, Judea, Egypt, Arabia, and Other Foreign Countries). On his travels, Belon was in the habit of investigating the birds and fishes that came to market, and in England he met the Venetian Daniel Barbaro, who had made many drawings of Adriatic fishes. From these sources Belon produced two books on fishes: L'Histoire naturelle des éstranges poissons marins (1551; The Natural History of Foreign Sea Fish) and De aquatilibus (1553). The first is notable for its dissertation on the dolphin, in which he identified the common Atlantic species with the dolphin of the ancients and distinguished it from the porpoise.

Belon's principal achievement is a history of birds, L'Histoire de la nature des oyseaux (1555; The Natural History of Birds). An illustrated book of the kind inspired by the drawings of Albrecht Dürer and Leonardo da Vinci, it describes about 200 birds, mostly of European origin. He drew attention to the correspondence between the skeletons of birds and man, an early hint of the discipline of comparative anatomy.

Belon was also interested in geology and botany and is reputed to have introduced the cedar of Lebanon into western Europe. He also established two botanical gardens in France and suggested that many exotic plants might be acclimatized and grown in temperate regions. In many ways a typical figure of the Renaissance, Belon's end was all too typical of that time, for he was murdered in the Bois de Boulogne in 1564.