Trefusis was the eldest son and heir of John Trefusis (d.1603) of Trefusis by his wife Mary Gaverigan, a daughter and co-heiress of Walter Gaverigan of Gaverigan, Cornwall. The Trefusis family (anciently de Trefusis) continue in 2015 as lords of the manor of Trefusis, from which they took their surname at some time before the 13th century.
He matriculated at Broadgates Hall, Oxford on 3 May 1605 aged 18 and was a student of law at the Inner Temple in 1607. He succeeded his father in 1603, inheriting several manors. In 1621 he was elected Member of Parliament for Truro in Cornwall. He was appointed High Sheriff of Cornwall for 1626–27.
Marriages & progeny
He married twice:
- Firstly in 1611 to Jane Trefry, the daughter of William Trefry of Place, Fowey, Cornwall, by whom he had 5 sons and 3 daughters, including:
- John Trefusis (1612-1654), eldest son and heir, who in 1638 married his step-sister Elizabeth Drake. His only son and heir was Francis Trefusis (1650-1680) who in 1672 married Bridget Rolle (1648-1721), the daughter of the wealthy Robert Rolle (c.1622-1660) of Heanton Satchville, Petrockstowe, Devon, by his wife Lady Arabella Clinton, the younger daughter, and in her issue the eventual heiress, of Theophilus Clinton, 4th Earl of Lincoln, 12th Baron Clinton (d.1667). The main connection of the Rolles with the southern part of Cornwall appears to be that in 1601 Robert Rolle (died 1633) of Heanton Satchville, Petrockstowe, Devon (a grandson of George Rolle (d.1552) of Stevenstone, founder of the Rolle family in Devon), purchased the manor of Callington in Cornwall, thereby gaining the pocket borough seat of Callington in Parliament, which in future served to promote the careers of many Rolles and descendants of that family. In 1794 Francis's great-great-grandson Robert George William Trefusis (1764-1797) of Trefusis, the senior representative of the family, successfully claimed the peerage title Baron Clinton following the death in 1791 without progeny of his grandfather's 3rd cousin George Walpole, 3rd Earl of Orford, 16th Baron Clinton (1730–1791), and thus became the 17th Baron Clinton. Both Walpole and Robert Trefusis were descended from the marriage of Robert Rolle (c.1622-1660) of Heanton Satchville, Petrockstowe, Devon, and Lady Arabella Clinton. His descendant Charles John Robert Hepburn-Stuart-Forbes-Trefusis, 21st Baron Clinton (1863–1957), the last in the senior male line, "held sway over the largest estate Devon had ever seen", mostly former Rolle lands, now managed by Lord Clinton's Clinton Devon Estates company.
- Secondly to Joan Strode, the widow of Sir Francis Drake, 1st Baronet (1588-1637) of Buckland Abbey, Devon, nephew and heir of Admiral Sir Francis Drake (1546-1596), and the 2nd daughter of Sir William Strode (1562-1637), of Newnham, in the parish of Plympton St Mary in Devon, seven times a Member of Parliament for Devon.
- Hunneyball, Paul, biography of Trefusis, John (c.1586-1647), of Trefusis, Mylor, Cornw. published in History of Parliament: House of Commons 1604-1629, ed. Andrew Thrush and John P. Ferris, 2010 
- Vivian, J.L., The Visitations of Cornwall: comprising the Heralds' Visitations of 1530, 1573 & 1620; with additions by J.L. Vivian, Exeter, 1887, pp. 463–8, pedigree of "Trefusis of Trefusis".
- Vivian, J.L., The Visitations of Cornwall: comprising the Heralds' Visitations of 1530, 1573 & 1620; with additions by J.L. Vivian, Exeter, 1887, pedigree of "Trefusis of Trefusis", pp.463-8, p.464 
- Trefusis descended to Major Hon. Henry Walter Hepburn-Stuart-Forbes-Trefusis of the Scots Guards, the second son of Charles Henry Rolle Hepburn-Stuart-Forbes-Trefusis, 20th Baron Clinton (1834–1904), and in 2015 the occupant of the manor house of Trefusis is the Major's grandson Nicholas John Trefusis (born 1943), Lieutenant-Commander Royal Navy, a Justice of the Peace for Cornwall and a Deputy Lieutenant for that county. (Kidd, Charles, Debrett's peerage & Baronetage 2015 Edition, London, 2015, p.259, Baron Clinton, Collaterals)
- Vivian, J.L., The Visitations of Cornwall: comprising the Heralds' Visitations of 1530, 1573 & 1620; with additions by J.L. Vivian, Exeter, 1887, pedigree of "Trefusis of Trefusis", pp.463-8 ; The first of the family to whom a date is assigned by Vivian, 1887, p.463 is "William Trefuses" who was living in 1291 (regnal date 22 Edward I), who was descended in the fourth generation from "Aceus de Trefuses", who is likely therefore to have been living in the 12th century
- Alumni Oxonienses
- Vivian, 1887, p.465
- Vivian, Lt.Col. J.L., (Ed.) The Visitations of the County of Devon: Comprising the Heralds' Visitations of 1531, 1564 & 1620, Exeter, 1895, p.655, pedigree of Rolle
- Hunneyball, Paul, "Callington Borough", published in History of Parliament: House of Commons 1604-1629, ed. Andrew Thrush and John P. Ferris, 2010 
- Lauder, Rosemary, Devon Families, Tiverton, 2002, p.67
- Lauder, p.73
|Parliament of England|
Thomas Burgess, junior
|Member of Parliament for Truro
With: Barnaby Gough
Sir John Catcher