Trained in law, Lenthall was chosen speaker of the House at the beginning of the Long Parliament in November 1640. When on Jan. 4, 1642, King Charles I personally entered the Commons to arrest five opposition leaders, Lenthall refused to reveal their whereabouts, uttering the famous words “May it please your Majesty, I have neither eyes to see nor tongue to speak in this place but as the House is pleased to direct me, whose servant I am here.” During the Civil Wars he sided with Parliament, and upon the outbreak (1647) of the power struggle between the Presbyterians and Independents he supported the Independents. At the same time he was probably secretly in sympathy with the Royalist cause.

Lenthall continued as speaker in the first Parliament (1654) held under Oliver Cromwell's Protectorate, and after the collapse of the Protectorate in 1659 he was speaker of the restored Long Parliament. Although he supported the Restoration of King Charles II in 1660, he was thereafter barred from public office. He soon gained royal favour by testifying against a man accused of participating in the trial and execution (1649) of Charles I.