On 15 April 1797, while at Bath, she met her future husband, William Wilberforce, to whom she had been recommended by Wilberforce's friend, Thomas Babington.
The couple were married at St Swithins Church, Walcot, Bath on 30 May 1797.She nearly died following an attack of typhoid in 1800, after which her health was never strong.
Nevertheless, she bore six children, all of whom survived to adulthood.
The children were William (July 1798), Barbara (1799), Elizabeth (1801), Robert (1802), Samuel (1805), and Henry (1807).
Her daughters predeceased her, Barbara dying in 1821 and Elizabeth in 1832.
Following her husband's death in 1833, Barbara Wilberforce spent her time with her sons, Robert and Samuel, or with her sister Ann Neale in Taplow in Buckinghamshire.
She is buried next to East Farleigh church, Kent, her son Robert Wilberforce's first living, and where her son Henry would minister a decade later.
In the 2006 film Amazing Grace, about her husband's involvement in the movement to eliminate the slave trade, she was portrayed by actress Romola Garai.