Clerk studied science at Andersonian College, Glasgow, and Yorkshire College, Leeds. He built a gas (hydrocarbon vapour) engine in 1876 and in 1881 patented his two-stroke engine. The principal difference between the Clerk cycle and the more common Otto cycle is that the Clerk cycle generates an ignition once every two strokes of the piston rather than once every four. Clerk also investigated extensively the properties and commercial uses of gas for heating and lighting.

In 1916 Clerk, a director of the National Gas Engine Company, was appointed director of engineering research for the British Admiralty; he was knighted in 1917. The results of his research are published in part in his book The Gas, Petrol, and Oil Engine (vol. 1, 1909; vol. 2, 1913).