Kalm was born in the province of Angermannia, the son of a Lutheran minister. He studied at the Academy of Åbo in Turku from 1735 and then Uppsala University from 1740, where he was a pupil of Carolus Linnaeus. In 1747 he was chosen by the Royal Swedish Academy of Sciences to travel to North America to find seeds and plants which might prove useful for agriculture or industry. Kalm arrived in Pennsylvania in 1748 and made his base of operations the Swedish ex-patriate communities in southern New Jersey, where he served as pastor of a local church and married in 1750. He made trips as far west as Niagara Falls and as far north as Quebec before returning to Sweden in 1751. After his return he taught at the Academy of Åbo until his death. He established a botanical garden in Turku.
Kalm's journal of his travels was published as En Resa til Norra America (Stockholm, 1753-1761). It was translated into English in 1770 as Travels into North America.