De la Beche entered the army but at the end of the Napoleonic Wars he chose to devote himself to geology instead. After traveling extensively in Europe and Jamaica on his own research work, he became, in 1835, director of the Geological Survey of Great Britain, which had been recently formed largely on his initiative. He was also instrumental in setting up the Royal School of Mines in 1851, of which he was the first principal.

He wrote extensively on the geology of southwest England and Jamaica, publishing the first account of the geology of Jamaica in 1827 and his report on the geology of Devon during the period 1832–35.

In 1834, while working in Devon, he made his most significant discovery. He observed that some rock strata contained fossil plants similar to those of the Carboniferous system, discovered by William Conybeare in 1822, but did not contain any of the fossils of the preceding Silurian system, recently discovered by Roderick Murchison. The Silurian was believed to merge directly into the Carboniferous and De la Beche assumed the strata he had discovered came before the Silurian. However, William Lonsdale, librarian of the Geological Society, convincingly argued for a system, later named the Devonian, which overlay the Silurian and underlay the Carboniferous.

De la Beche wrote extensively on geology; his A Geological Manual (1831), How to Observe (1835), and Geological Observer (1851) were in part aimed at satisfying the growing popular interest in geology.