The Byron Residence was built by Frank Byron in 1917, who then occupied it with his brother James Byron. At the time, the pair ran the local Byron Bros. grocery store. However, in 1924, James relocated to Norton to start a career as a real estate broker. Frank also quit the grocery store to work as a carpenter and eventually became foreman of the National Harbour Board. After James left, Frank continued to live in this house until the 1960s. Notably, as with many of the early occupants of Clarendon Street, the brothers were devout Catholics who attended the local St. Peter's Parish.

The Byron Residence is notable for its presence in the Douglas Avenue Preservation Area. This Saint John streetscape is recognized and protected for its integration of the lower, middle, and upper classes. Built in the mid-1850's, Douglas Avenue was designed to connect the new suspension bridge at Reversing Falls to Saint John's Main Street. Thanks to its richly interconnected community, due in part to the spacious front lawns on the numerous properties, this avenue and some of the surrounding residential streets were highly popular during the late 1800s. Additionally, when streetcar transportation became accessible to Douglas Avenue in 1902, more and more members of the working class were drawn to the area.

The first block of Clarendon Street, which was established in 1909 and on which this house sits, is considered a part of the Douglas Avenue Preservation Area. Clarendon Street is recognized for its numerous Craftsman, Arts and Crafts, and other post-Victorian houses, and the Byron Residence, with its Craftsmen-style design, two-storey rectangular form, and front veranda, fits in perfectly with the surrounding buildings.

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