One of the oldest publishers in the United States, Henry Holt and Company was initially founded as Leypolt and Holt in 1866 by Henry Holt (1840-1926) and Frederick Leypoldt (1835-1884), a Philadelphia bookstore owner who had became interested in publishing translations and reprints of European titles. The firm briefly changed its name to Leypoldt, Holt and Williams in 1870 and again to Holt and Williams in 1871, when Leypolt left to concentrate on the compilation of a publication that ultimately became Publisher's Weekly. In 1873, Holt began publishing without partners as Henry Holt and Company. Alfred Harcourt (later of Harcourt, Brace, Jovanovich) was trade editor between 1910 and 1919.

The firm achieved great success in the publication of its Leisure Hour hardcover novel series and Leisure Moment paperback series, and published a wide range of European and American fiction. Holt's firm belief that non-fiction publication was the key to success in publishing is reflected in the firm's lists, which included the work of many prominent American scientists and social scientists. It did, however, publish works by many internationally renowned authors, including Erich Fromm, Robert Frost, Hermann Hesse, Norman Mailer, Herta Müller, Thomas Pynchon, Robert Louis Stevenson, Ivan Turgenev, and H.G. Wells. It also published the first American editions of a number of Australian novels, including Henry Handel Richardson's (q.v.) The Fortunes of Richard Mahony in 1917.

For a time, the company published the magazine Field and Stream. It also published under several imprint titles, including Metropolitan Books, Times Books, Owl Books, and Picador, as well as under the name of Holt Paperbacks.

In 1960, Henry Holt and Company merged with the Rinehart (New York) and Winston (Philadelphia) publishing houses to form Holt, Rinehart and Winston. CBS purchased that company in 1967 but, in 1985, sold the retail publishing division to the German-based Georg von Holtzbrinck Publishing Group. The firm's name subsequently reverted back to the Henry Holt Company. The educational publishing arm, which retained the Holt, Rinehart and Winston name, was sold to Harcourt Brace Jovanovich. When owner Reed Elsevier sold Harcourt to Houghton Mifflin in 2007, Holt, Rinehart and Winston was combined with McDougal Littell to form Holt McDougal.