Holt, Rinehart and Winston was formed in New York in 1960 by a merger of publishers Henry Holt and Company (formed in 1866 as Leypolt and Holt), Rinehart and Company, and the John C. Winston Company of Philadelphia. Former Holt president Edward T. Rigg was appointed chairman and chief executive officer. Charles F. Kindt (Winston president) and Stanley M. Rinehardt (Rinehart president) were both made senior vice-presidents, while Alfred C. Edwards became president and chief administrative officer.

Among the new company's earliest publications were Robert Ruack's The Old Man's Boy Grows Older (1961) and Kurt Vonnegut's Cat's Cradle (1963). Australian author Christina Stead (q.v.) had The Man Who Loved Children reprinted by Holt, Rinehart and Winston in 1965. The following year, the company published her Dark Places of the Heart, Stead's first new novel in fourteen years. Her novels The Puzzleheaded Girl (1967) and The Little Hotel (1973) were also first published by Holt, Rinehart and Winston. The 1960s also saw the publication of such as titles as I Never Promised You A Rose Garden (a 1964 best-seller by Hannah Green); God Bless You, Mr Rosewater (1965, by Kurt Vonnegut); and Night Falls on the City (1967, by Sarah Gainham). During the 1960s, Holt, Rinehart and Winston also established the Winston Science Fiction series, Rinehart Editions, Rinehart Suspense Novels, and the Rivers of America series.

In 1967, the company was bought out by CBS. This led to a number of senior personnel changes, which created an air of instability within the company. The result was a decline in its publishing output that lasted until the mid-1970s. One of Holt, Rinehart and Winston's more successful authors around this period was Erica Jong, whose best-seller Fear of Flying was published in 1973. Jong also had several books of poetry published by the company between 1971 and 1976, before her follow-up novel, How to Save Your Own Life, was released in 1977.

In addition to its fiction titles, Holt, Rinehart and Winston has published comic-strip anthologies, including Peanuts by Charles Shultz and Doonesbury by G. B. Trudeau, as well as numerous non-fiction titles by authors such as Karl Barth, Phillip Berrigan, Erich Fromm, and Maria Montessori.

In late 1985, CBS sold the Holt, Rinehart and Winston trade publication division to Verlagsgruppe Georg von Holtzbrink (Stuttgart, Germany), but retained the firm's school and college divisions. Under Holtzbrink, the publishing house returned to one of its pre-1960 trade names: Henry Holt and Company. The Holt, Rinehart and Winston education division was sold by CBS to Harcourt Brace Jovanovich in 1986, and its headquarters were subsequently relocated to Austin, Texas. The company continued to maintain its reputation was one of America's leading secondary education publishers, specialising in languages, arts, science, social studies, and maths until 2007, at which time Harcourt was sold to Houghton Mifflin. As a result of this acquisition, Holt, Rinehart and Winston was combined with McDougal Littell to form the new company, Holt McDougal.