Originally opened as a boarding house in 1845, the hotel played a vital role leading up to the 1916 Easter Rising and other significant Irish events.

[4] Wynn's hotel was the venue for a meeting of Irish nationalists, held on 11 November 1913 (1913-11-11), with a view to forming an armed body.

The meeting was arranged by Bulmer Hobson and The O'Rahilly, and chaired by Eoin MacNeill which resulted in the creation of the Irish Volunteers.

[7] During the Easter Rising of April 1916, the hotel was burned to the ground as it was set on fire by incendiary bullets which were hitting a street barricade erected outside.

Guests and staff were accommodated in the Clarence Hotel located on the opposite side of the River Liffey on Wellington Quay.