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Sedgwick was the son of the vicar of Dent in England. He graduated in mathematics from Cambridge University in 1808, was made a fellow in 1810, and was elected to the Woodwardian Chair of Geology in 1818, a post he retained until his death. He was made president of the Geological Society in 1829.

In 1831 he began a study of the Paleozoic rocks of Wales, choosing an older region than the Silurian recently discovered by Roderick Murchison. In 1835 he named the oldest fossiliferous strata the Cambrian (after Cambria, the ancient name for Wales). This immediately caused a problem for there was no reliable way to distinguish the Upper Cambrian from the Lower Silurian.

Sedgwick formed a close friendship with Murchison. The two made their most significant joint investigation with their identification of the Devonian System from studies in southwest England in 1839. The partnership between Sedgwick and Murchison was broken when Murchison annexed what Sedgwick considered to be his Upper Cambrian into the Silurian. The bitter dispute between the two over these Lower Paleozoic strata was not resolved until after Sedgwick's death, when Charles Lapworth proposed that the strata should form a new system – the Ordovician.

Sedgwick's works included A Synopsis of the Classification of the British Paleozoic Rocks (1855). In 1841, largely due to Sedgwick, a museum now bearing his name was opened to house the growing geological collection. Sedgwick was, throughout his life, a committed opponent of Darwin's theory of evolution.