Manning joined his father's firm, taking control after his father's death in 1791. He was elected a Director of the Bank of England from 1792 to 1831 and its Governor between 1812 and 1814, having served as its Deputy Governor from 1810 to 1812.
Around the same time, he and several other merchants lobbied Secretary for Colonies William Huskisson for exclusive trading rights with New Zealand.[5] A "William Mannings" is listed as a director of the New Zealand Company in 1825, a venture chaired by the wealthy John George Lambton, Whig MP (and later 1st Earl of Durham), that made the first attempt to colonise New Zealand.[6][7][8]
He married twice; firstly Elizabeth, daughter of banker Abel Smith of Nottingham, with whom he had two daughters and secondly Mary, daughter of barrister Henry Lannoy Hunter of Beech Hill, Reading, Berkshire with whom he had four sons and four daughters.
After the death of Lord Frederick Campbell in 1816, he bought Combe Bank near Sevenoaks, Kent from Campbell's daughter. However, he got into financial difficulties in the 1820s and had to declare himself bankrupt in 1831. He was forced to resign from the Bank of England, sell his estates and move to a smaller property in Gower Street, London.
William Manning died at Gower Street in 1835 and was buried at Sundridge, Kent.