Penington was the son of Robert Penington and followed him in becoming a Liveryman of the Worshipful Company of Fishmongers. He inherited several estates from his father and purchased one of his own. He made a fortune as a wine and cloth merchant. From 1626 he acted as financial agent to his second cousin, Admiral John Penington. He increased his commercial holdings in 1629 by becoming a partner in the brewery business of his second wife's family. He and his wife, Mary, the widow of Roger Wilkinson, a Citizen of the City of London, were both staunch Puritans.