In 1622 he rallied the defence of Jamestown which was attacked by Native Americans, during which the lives of some 400 settlers were lost and he then oversaw the contraction of the colony from scattered outposts into a defensive core.

[5] He was born at Boxley Manor in Kent, and attended St Mary Hall, Oxford, (from 1 July 1603) and Gray's Inn (1604).

[7][4] Wyatt had dealings with Nemattanew and leader Opechancanough, during a time of strife and also leading up to the Indian massacre of 1622.

[9][10] At the same time, Wyatt was described as an ancient planter (which entitled him to land patents), and owned at least 500 acres near Blunt Poynt.

[4] After leaving office, Wyatt left Virginia for Ireland and England to settle his father's estate.

His great-grandfather Thomas Wyatt the elder, the poet, was briefly imprisoned in the Tower of London for an alleged relationship with Anne Boleyn.

[12] His younger brother, the Reverend Hawte Wyatt (1594–1638), who was the rector of Maidstone, Kent, travelled to Virginia with Francis in 1621 and returned with him to England in 1624 after their father died.