Thomas served with distinction under his relative the Lord Protector Edward Seymour, 1st Duke of Somerset at the Battle of Pinkie Cleugh in 1547; but in 1551 he was one of the peers who condemned Somerset to death on a charge of felony.
He was a trusted counsellor of Mary I of England, who appointed him deputy of Calais. Wentworth was the last Englishman to hold this post, for on 7 January 1558 he was compelled to surrender Calais to Francis, Duke of Guise, his representations as to the defenceless condition of the fortress having been disregarded by the Privy Council some years earlier. He was judged harshly for his ineptitude and indecision during the final crisis, and was even accused of treason. In fact his passive behaviour was probably due to his certainty that the cause was hopeless. His behaviour was unkindly compared to the gallant defence of Guisnes, yet Guisnes also surrendered after a few days.
Wentworth himself remained in France as a prisoner of war for more than a year, and on his return to the Kingdom of England in 1559 he was sent to the Tower of London for having surrendered Calais. He was eventually acquitted of treason. He died on 13 January 1584.
His eldest son William Wentworth married Elizabeth Cecil (born 1 July 1564), a daughter of William Cecil, 1st Baron Burghley, but predeceased his father on 7 November 1582. The peerage consequently passed to his second son Henry Wentworth, 3rd Baron Wentworth (1558-1593), who was one of the judges of Mary, Queen of Scots, at Fotheringay in 1586. Henry was married to Anne Hopton and was father to Thomas Wentworth, 1st Earl of Cleveland.