Botherum was built for Madison C. Johnson in 1850 or 1851 (sources vary) by John McMurtry, a well-known architect and builder based in Lexington. The house was intended, in part, as a shrine to Johnson's late wife Sally Ann, a sister of Cassius Marcellus Clay who died giving birth in 1828. Although McMurtry was known for his Gothic Revival architecture, and is credited with establishing the popularity of that style in central Kentucky, Botherum shows an unusual combination of Greek, Roman, and Gothic architectural elements.