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.
[4] In the following year, he was returned for Lostwithiel, a seat he held until his death on 3 April 1730.
[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.