Located at the corner of School Street and Tremont, not far from the seat of the Massachusetts state government, the hotel has long been a rendezvous for politicians.

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.[4] 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.

[4][3] 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.

[3] On May 31, 1884, when founder Harvey Parker died at the age of 79, he was buried in Mount Auburn Cemetery, the “permanent home” of many of Boston's most prestigious people.

James Michael Curley, the charismatic, Irish-American "Mayor of the Poor" who dominated Boston politics for the first half of the twentieth century, was a constant presence at the Parker House, in part because Old City Hall stood directly across from the hotel on School Street.

[4] John F. Kennedy announced his candidacy for Congress at the Parker House in 1946 and also held his bachelor party in the hotel's Press Room there in 1953.

[3] Then Senator Kennedy also proposed to his future wife, Jackie Bouvier, at Table 40 in Parker's Restaurant located inside the hotel.

[10] In 1996, the Omni Hotels chain and its properties, including the Parker House, were sold to TRT Holdings, owned by Texas billionaire Robert Rowling.

Harvey D. Parker, a coachman for a Watertown woman, frequently dined in a cellar cafe owned by John E. Hunt whenever he visited Boston.

A typical menu from the chef could include, mock turtle soup, boiled turkey in oyster sauce, ham in champagne, and much more.

The original recipe had more distinctly French details, like a rum glaze brushed onto the cake layers and slivered almonds around the sides.

Although many "haunting" books and "ghost tours" claim that Stephen King's 1999 short story 1408—about a writer who experiences a haunted stay at a New York hotel called the Dolphin—was based on Room 303 of the Parker House and the supernatural events surrounding the room, King's personal assistant says that claim is false.

[4] In March 1877, humorist Mark Twain was staying at the Parker House in room 168. and observed to a reporter, "You see for yourself that I'm pretty near heaven—not theologically, of course, but by the hotel standard.

"[4] Twain's quote inspired the title for the definitive history of the Parker House, Heaven, By Hotel Standards, written by Susan Wilson and most recently published in 2019.