Fieser was born in Columbus, Ohio, obtained his BA in chemistry in 1920 from Williams College, and his PhD under James Bryant Conant at Harvard in 1924. With his research assistant and wife Mary Peters Fieser (MA, 1936, Radcliffe) he coauthored eight books and the first seven volumes of the classic series Reagents for Organic Synthesis known popularly among chemists as "Fieser and Fieser".
Fieser had two chemical reagents named for him. Fieser's reagent is a mixture of chromium trioxide in acetic acid. Fieser's solution is an aqueous solution of potassium hydroxide, sodium hydrosulfite, and sodium anthraquinone b-sulfonate. Woodward's rules for calculating UV absorption maxima are also known as the Woodward-Fieser rules.
Dow Chemical began producing his formula for napalm during World War II. But it was not until the Vietnam War that the use of the jellied gasoline stirred controversy. Fieser, however, was unapologetic for its creation. He stated, "I have no right to judge the morality of napalm just because I invented it.