Springing from a family of courtiers, including some of infamous reputation, Francis Wyatt became the first English royal governor of the Virginia colony. Prior to 1621, the colony was largely organized, maintained, and governed by private business, specifically the Virginia Company of London. Upon the demise of that organization, by 1625 the crown assumed full control and appointed Wyatt to travel to Jamestown and inspect the colony's development and state.

Wyatt brought with him the first written constitution for an English colony. However, the colonials had only two years earlier established an Assembly, where certain ground rules were discussed and put into place. Wyatt wisely incorporated colonial wishes into the official document sent by the crown, and helped to establish the Jamestown assembly into a true governmental body. Wyatt was in his position for less than one year when he had to assume a crisis leadership role.

The colony was attacked by Indians. More than 400 English settlers perished and the colonial social structure was in further disarray. Wyatt immediately oversaw the gathering of the remaining settlers into a smaller, more structured and safer settlement, where defense was stronger.

Wyatt had received a thorough education in England. His birth to a prominent family assured he would study at Oxford, and later read law at Grey's Inn. He was also knighted several years before he left for Virginia. He remained in his position of royal governor until 1625, when Sir George Yeardley took office. Wyatt remained in Jamestown after his tenure as governor ended. He lived there with his wife, brother, and seventeen servants. Soon, however, his interests in Europe beckoned, and he returned to Ireland and England to settle his father's estate. It was while he was here that he learned he had been appointed royal governor of the Virginia colony once again.

He returned to Jamestown and served as governor from 1649 until early 1641. At that time he returned once again to England, where he died three years later. Wyatt descended from Thomas Wyatt, who was once imprisoned in the Tower of London, under accusation of having an affair with Anne Boleyn. That Wyatt's great-grandson, Thomas Wyatt the younger, led Wyatt's rebellion, which sought to replace Queen Mary with her half-sister, Elizabeth.

Francis Wyatt was married to Margaret, the niece of Jamestown's treasurer, George Sandys. The couple had at least two children, Henry and Francis, the latter of whom attended King's College at Cambridge University.