The hotel was home to the Saturday Club, which met on the fourth Saturday of every month, except during July, August, and September. Among the Saturday Club’s nineteenth-century members were poet, essayist, and preeminent transcendentalist Ralph Waldo Emerson, poet and The Atlantic Monthly editor James Russell Lowell, novelist Nathaniel Hawthorne, poets John Greenleaf Whittier and Henry Wadsworth Longfellow, diplomat Charles Francis Adams, historian Francis Parkman, and sage-about-town Dr. Oliver Wendell Holmes, Sr.
Charles Dickens resided in the Parker House for five months in 1867–1868 in his own apartments; he first recited and performed "A Christmas Carol" for the Saturday Club at the Parker House, then again for an adoring public at nearby Tremont Temple. The Parker House kept the door to Dickens' guest room when he stayed in 1867 and the mirror used by him for rehearsals.
The hotel introduced to America what became known as the European Plan. Prior to that time, American hotels had included meals in the cost of a room, and offered them only at set times. The Parker House charged only for the room, with meals charged separately and offered whenever the guest chose.
Actor John Wilkes Booth stayed at the hotel April 5–6, 1865, eight days before assassinating Abraham Lincoln. He was apparently in Boston to see his brother, actor Edwin Booth, who was performing there. While in Boston, Booth was seen practicing at a firing range near the Parker House.
Between 1866 and 1925, the hotel increased in size with new stories and additions, eventually expanding its footprint over 41,400 square feet of land—the bulk of the city lot bordered by Tremont, School, and Bosworth Streets and Chapman Place.
The Parker House created Massachusetts’ state dessert, Boston Cream Pie; invented the Parker House roll; and coined the word "scrod," which is not a kind of fish, but a term for the freshest, finest, and youngest white fish of the day.