Cottrell taught chemistry at the University of California, Berkeley, from 1902 to 1911 and began his work on electrostatic precipitators in 1906. In 1912 he founded the Research Corporation, a nonprofit organization that supports basic research in colleges and universities, and he assigned his precipitator patents to the corporation as an endowment.

From 1911 to 1920 Cottrell was associated with the United States Bureau of Mines as chief physical chemist, chief metallurgist, and finally director. He helped develop the process of separating helium from natural gas and participated in the creation of the bureau's mine-safety division. He was director (1922–27) of the Fixed Nitrogen Research Laboratory of the U.S. Department of Agriculture, where he helped develop the synthetic ammonia industry in the U.S. on the basis of the Haber–Bosch process.