Branton Holstein Henderson was born in Norristown, Pennsylvania, in 1823. In 1827, Branton moved to Mercer, Pennsylvania, with his mother, Elizabeth Henderson, and his brother, Samuel Holstein Henderson following the death of his father. He attended Allegheny College in Meadville, Pennsylvania, and later moved to New Castle, Pennsylvania, with his mother.
Branton was engaged in a number of business endeavors throughout his life, some of which involved coal, iron, horses, and the construction of furnaces. He seemed to have an especially close relationship with his nephew, Matthias Holstein Henderson, who lost both of his parents before reaching adulthood. As a young man, Matthias worked at a store owned by Branton, and would later follow his uncle in other professional and personal pursuits. After Elizabeth's death in 1871, Branton and Matthias relocated to Sharon, Pennsylvania, and worked for the First National Bank of Sharon, where they would become vice presidents. Both were also prominent Freemasons, with Matthias reaching the rank of Grand Master.