After returning to Britain, Playfair became manager of a calico works in Primrose, near Clitheroe, and in 1843 was appointed Professor of Chemistry at the Royal Manchester Institution, where he was assisted by Robert Angus Smith.
Appointed a Companion of the Order of the Bath that same year, Playfair also became Gentleman Usher to Prince Albert, and in 1853 was appointed Secretary of the Department of Science, in which capacity he advocated the use of poison gas against the Russians in the Crimean War.