A Union Army veteran of the American Civil War, Comstock began about 1872 to work with the Young Men's Christian Association in New York City. In 1873 he lobbied successfully for the enactment of a severe federal statute known as the Comstock Law (Comstock Act), which outlawed the transportation of obscene matter in the mails. From that year until his death he served (without pay until 1906) as a special agent of the U.S. Post Office Department. Also in 1873 he founded the New York Society for the Suppression of Vice.

Ordinarily, Comstock attacked commercial pornography rather than serious writing, but he sometimes took action against established modern works and the classics on the principle of “morals, not art or literature.” Personally vindictive toward “libertines,” he is said to have boasted of the number of persons he had driven to suicide. More creditable were his efforts to suppress fraudulent banking schemes, mail swindles, and medical quackery.