As St Enoch station opened in 1876, construction of the hotel began. Given the size and grandeur of the building, construction was remarkably quick, and the St Enoch Hotel opened on July 3rd 1879. With 200 bedrooms and 20 public rooms, it was the largest of the city's three railway hotels.

The imposing frontage facing St Enoch Square was 360ft long and 120ft high and the north wing, extending to Dunlop Street was 500ft long.

By the 1970s, the St Enoch, like Glasgow's other railway hotels, the North British and Central, had seen better days, much of their business now coming from hiring out its public rooms for trade receptions. Lack of compliance with modern fire regulations hastened the end and the St Enoch Hotel closed in 1974. In act of architectural vandalism, remarkable even for Glasgow, the hotel was demolished and a second rate shopping mall erected.