Henry Oscar Houghton was born in 1823 in Sutton, Vermont. The second youngest of twelve children, Houghton was raised under frugal circumstances. He became an apprentice at the Burlington Free Press at age thirteen and eventually learned the trade of compositor, or typesetter. Houghton worked his way through the University of Vermont. Upon graduation, he moved to Boston where he found employment first as a reporter, then as a proofreader for the well-known Dickinson Type Foundry, and later as a freelance proofreader.

Houghton eventually accepted a job offer from a small Cambridge firm, Freeman & Bolles, where a great number of books from Little, Brown and Company were set and printed. Houghton was offered a partner's share of the business when Freeman retired and, although he had no capital of his own, he seized the opportunity. In 1849, Houghton's share of the firm was equal to the annual wages of eight compositors. It amounted to 3,200 dollars—an immense sum in those days. Houghton, a compositor himself just a few years before, was not yet twenty-six years old.

When Bolles left the firm, Houghton became the sole decision maker. He moved the business to the banks of the Charles River in 1852, and from then on it was aptly named the Riverside Press. Henry Houghton built a reputation for himself as a student of his craft and a demanding perfectionist. His diligence earned the esteem of Ticknor & Fields whose impressive list of authors, such as Hawthorne and Longfellow, were printed primarily by Riverside. The culmination of Houghton's success came in 1863, when he was hired by G. & C. Merriam Company for the printing and binding of their new dictionary.

In 1864, Henry Houghton formed a partnership with Melancthon Hurd, a member of a New York publishing firm. Hurd & Houghton established itself quickly and new business began trickling into the Riverside Press from New York. Within three years, Hurd & Houghton increased its workforce from ninety to three hundred to accommodate the new orders.

George Harrison Mifflin was admitted to partnership at the Company in 1872. Mifflin's energetic, boisterous nature perfectly complemented Houghton's, and the Harvard graduate held unswerving devotion and respect for his senior partner. When Houghton became mayor of Cambridge, Mifflin took over as head of the Press. In 1880, the firm became Houghton, Mifflin and Company.

The Riverside Press enjoyed continued success and was recognized for typographic and artistic excellence with medals at the Philadelphia Centennial Exposition and the Paris Exposition of 1878. In 1881, Publishers Weekly hailed Houghton as the American printer par excellence. By 1886, Henry Houghton's Riverside Press had grown to a staff of six hundred with thirty-three presses and seven thread-sewing machines.

At the time of his death, Henry Oscar Houghton was widely eulogized as a master printer and an enterprising publisher. George Mifflin assumed the reins as president, and young Harry Houghton, who began work at the Press in 1877, became head of Riverside.