Blackwell was born in England, the son of Bristol sugar refiner Samuel Blackwell (c. 1790–August 7, 1838) and Hannah Lane, who moved their family of eight children to the United States in 1832.
Samuel Blackwell senior, an anti-slavery campaigner and Congregationalist who wanted his daughters educated as well as his sons, passed his interest in social reform on to his children.
Samuel Charles Blackwell's wife was Antoinette Brown, the first woman ordained in a recognized church in the United States, and prominent speaker in the Abolitionism and Women's Rights Movements.
At that time, Blackwell was in the hardware business and also invested in real estate.
His brother, Henry B. Blackwell, was the husband of Lucy Stone, a friend of Antoinette Brown at Oberlin College.