Knatchbull was the eldest son of Sir Thomas Knatchbull, 3rd Baronet and his wife Mary Dering, daughter of Sir Edward Dering, 2nd Baronet.[2]
In 1702, Knatchbull was elected Member of Parliament for Rochester and held the seat to 1705.[3] In 1712, he succeeded his father in the baronetcy.[1] In 1713, he was elected MP for Kent and represented the constituency until 1715. He was elected MP for Kent again in 1722 and held the seat until 1727.[4] In the following year, he was returned for Lostwithiel, a seat he held until his death on 3 April 1730.[5]
Knatchbull married Alice Wyndham, daughter of Colonel John Wyndham and sister of Thomas Wyndham, 1st Baron Wyndham before 1698.[6] They had eight children, three daughters and five sons.[2] Knatchbull died at Golden Square in Middlesex and was succeeded in the baronetcy by his oldest son Sir Wyndham Knatchbull-Wyndham, 6th Baronet. His second son Edward sat in the Irish House of Commons and became later the 7th Baronet.