George was educated at home under private tutors, and afterwards assisted his father in the production of illustrated works on natural history.

On the latter's death in 1822, he and his brother James De Carle Sowerby continued their father's work on fossil shells, publishing the latter parts of the Mineral Conchology of Great Britain.

He published about 50 papers on molluscs and started several comprehensive, illustrated books on the subject, the most important the Thesaurus Conchyliorum, a work that was continued by his son, George Brettingham Sowerby II and his grandson George Brettingham Sowerby III.

He died at Hanley Road, Hornsey, on 26 July 1854 and is buried on the west side of Highgate Cemetery.

He wrote for Reeve's popular handbooks 'Popular Mineralogy,' London, 1850, and illustrated various books such as Flora Homoeopathica of Edward Hamilton which appeared in 1852–53.