On February 6, 2019 The Bluegrass Trust for Historic Preservation ventured to 21C Museum Hotel for their monthly deTour. In 2006 founders Steve Wilson and Laura Lee Brown upended the travel industry with the first of what would become a chain of boutique museum hotels, each paying homage to 21st century art with 24-hour museums incorporated into their layouts. In stark contrast to ‘big box’ hotel chains, Steve and Laura Lee own each and every piece housed in the museums, thoughtfully curating the collections and rotating them between locations every 6-8 months. Following Louisville (first) and Cincinnati (second), Lexington is home to the company's fifth location, joining (in order) Bentonville, Durham, Oklahoma City, Nashville, and Kansas City, with Chicago (2019) and Des Moines (2021) up next.

Known as Lexington’s first skyscraper, 21C’s Lexington location consists of 83 rooms and 5 suites spread out among 12 of the former Fayette National Bank tower’s 15 floors, originally constructed from 1913-1914 by renowned architecture firm McKim, Mead & White. In 1933 First National Bank acquired the tower and two adjacent buildings – each constructed circa 1870 – and added the vault, which is now nestled within the museum hotel’s upscale restaurant, LockBox. Around 1975 an architecture firm assumed ownership of the first floor and won an adaptive reuse award for their efforts, covering up the entirety of the original marble flooring in the process – not to worry, 21C was quick to unearth it, albeit significant damage had been inflicted by the former tenants – meanwhile the upper floors were used to house over 200 offices of various businesses. 21C announced their plans to purchase the three buildings in 2012 and officially opened in 2016, managing to not only maintain the original exterior facades​, but also pay tribute to the joining of the spaces and their combined history with hidden details throughout the interior.