George Mifflin was raised in one of the most affluent families in Boston, attending Boston Latin School and Harvard University and enjoying the luxuries afforded to the wealthiest groups of the time. Although this upbringing represented a sharp contrast to that of Henry Houghton, Mifflin was finally able to gain the printer's trust after several interviews at the Old Corner Bookstore in Boston. He went on to work in almost every position at Houghton's Riverside Press before becoming a partner in 1872.

Mifflin's energetic character and loyalty earned him Houghton's respect and led him to become head of the Press in 1872, when Houghton was appointed mayor of Cambridge. Mifflin poured himself wholeheartedly into his work. He became president of Houghton Mifflin after the death of Henry Houghton in 1895, and brought many new successes to the Company. Mifflin applied the attention to detail that he learned from his former partner to successfully reproduce scores of classic titles. He led the Company through a major transition as enrollment in public schools grew throughout the late 1800s and educational publishing surpassed trade and became its principal focus.

At the time of Mifflin's death in 1921, Houghton Mifflin's business had more than tripled, the capacity of the Riverside Press had doubled, and book sales had soared to more than three million dollars. Though Mifflin had gradually given control of various aspects of the Company to his most trusted employees, he remained proud that he had helped to bring the work of his mentor, Henry Oscar Houghton, to such grand fulfillment.

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