Daniel Henry Holmes opened on October 15, 1849, one of the most important additions to New Orleans, the D.H. Holmes department store. The store operated at the same location for 140 years and became a local treasure, as well as gained a national reputation as one of the outstanding retail establishments in the United States. The City of New Orleans and Historic Restoration Inc. joined together on a common mission, to preserve and readapt the use of this historic building by turning it into a truly unique 251-room luxury hotel.

The hotel opened in April 1995. The transformation of the pre-Civil War landmark into a 20th century hotel included a complete interior renovation and exterior restoration to the building.

The famous "clock", which was a favorite meeting place for generations of New Orleanians was missing since the stores closing in 1989. The clock was returned to the hotel in November of 1995. The clock presently hangs in its original location on Canal Street. Underneath the clock is the life size bronze sculpture of Ignatius Reilly, funded jointly by the hotel and the Downtown Development District. The statue mimics the opening scene of the 1981 Pulitzer Prize winning novel, A Confederacy of Dunces.