Smirke was the son of portrait painter Robert Smirke, and studied architecture as a pupil of classical architect John Soane in 1796, the same year he commenced his studies at the Royal Academy. He also studied and travelled in southern Europe for several years.
Smirke designed public buildings in the classical style, among the most famous being those still standing in London, including:
Of those no longer extant, he also designed:
Domestic buildings include alterations to Luton Hoo, Bedfordshire, and Hardwicke Court, near Gloucester. His domestic buildings in the neo-Gothic style include Lowther Castle in Cumbria, his first job in 1806 when he was 25, and Eastnor Castle, Ledbury, Herefordshire, designed in the early 19th century.
Together with John Nash and Sir John Soane, he became official architect to the Office of Works in 1813. He advised the Parliamentary Commissioners on the building of new Churches from 1818 onwards, contributing four himself, including St George, Brandon Hill in Bristol.