He was second surviving son of Thomas "Customer" Smythe of Westenhanger Castle in Kent, by his wife Alice, daughter of Sir Andrew Judde.

His grandfather, John Smythe of Corsham, Wiltshire, was described as yeoman, haberdasher and clothier, and was High Sheriff of Essex for the year of 1532.

[4] When the East India Company was formed in October 1600, Smythe was appointed as its first governor by the charter dated 31 December, a position he held for only four months.

Later that year he was re-elected to Parliament for Dunwich in place of Sir Valentine Knightley, who was chosen to sit for Northamptonshire.

[7] After one of his sons married intro the aristocracy, Smythe became part of the "court faction" along with Robert Rich, 2nd Earl of Warwick.

Sailing from Gravesend on 13 June 1603, his party arrived at Arkhangelsk on 22 July, and was taken by way of Kholmogory and Vologda to Yaroslavl, where the tsar was.

To address the new colony's many problems, Smythe ordered both the end of religious conversion of the Native Americans and the expansion of the tobacco crop.

[10] Parliamentarians urging the graft investigation included Nicholas Ferrar (Smythe's former deputy) and Edwin Sandys.

The King's officials continued to consult Smythe on all important matters relating to shipping and to eastern trade.

William Baffin named Smith Sound between Greenland and Ellesmere Island to honour the patron of his 1616 voyage of discovery.

In January 1618–19, Smythe was appointed one of the commissioners for the settlement of the differences with the Dutch which, however, after years of discussion, remained for the time, unsettled.

An engraving by Simon Pass is inserted in the Grenville copy of Smith's Voiage and Entertainment in Rushia (London, 1605).