He was the eldest son and heir of John III Killigrew (d1567) of Arwenack, the first Governor of Pendennis Castle appointed by King Henry VIII, by his wife Elizabeth Trewennard, 2nd daughter of James Trewennard of Trewennard, in the parish of Street Erth, Cornwall.
He was Member of Parliament for Lostwithiel in 1563 and twice for the family"s pocket borough of Penryn, in 1571 and 1572. Although appointed a commissioner to enquire into piracy, he was himself a notorious pirate and smuggler. In 1556 he was imprisoned by Mary with his father in the Fleet, but released after three weeks.
He became notorious for engaging in cattle theft, "evil usage in keeping of a castle" and as a Justice of the peace for abuses in arranging the quarter sessions.
Having been appointed a Commissioner to inquire into piracy, he himself was heavily engaged in that activity and traded with smugglers and pirates who frequented the waters around Arwenack. He was the subject of an official investigation in 1565.
