Cajori emigrated to the United States in 1875 and taught at Tulane University in New Orleans (1885–88) and at Colorado College (1889–1918), where he also served as dean of the department of engineering (1903–18). In 1918 he became professor of the history of mathematics at the University of California, Berkeley.

His major works include A History of Mathematics (2nd ed. 1919), A History of Mathematical Notations, 2 vol. (1928–29), A History of Physics in Its Elementary Branches (1899), William Oughtred, a Great Seventeenth-Century Teacher of Mathematics (1916), and The Chequered Career of Ferdinand Rudolph Hassler (1929). His revised translation of Sir Isaac Newton's Principia was published posthumously in 1934.