He was born at Allington Castle, the only son of Sir Thomas Wyatt, a poet, by Elizabeth Brooke, daughter of Thomas Brooke, 3rd Lord Cobham. The Duke of Norfolk was his godfather. At the age of fifteen he became a squire at the court of King Henry VIII, and Joint Constable of Conisborough Castle. He married Jane Hawte, daughter and co-heiress of Sir William Hawte of Bishopsbourne, by whom he had several children.
He was brought up a Roman Catholic. On his father's death in 1542, he inherited Allington Castle and Boxley Abbey. He served in the war against France, and was knighted in 1547. During the reign of King Edward VI, he was arrested, along with Henry Howard, Earl of Surrey, for breaking windows while drunk. They were tried before the Privy Council and were imprisoned in the Tower of London. On his release, Wyatt went to fight for King Carlos V of Spain in Flanders, obtaining further valuable military experience.
In 1543 he took part in the siege of Landrecies, and in the following year was at the siege of Boulogne. Returning to Allington, he lived quietly until the uprising by the Duke of Northumberland, to put Lady Jane Grey on the throne. Escaping punishment by Queen Mary, he took no well further part in politics until Mary's plans to marry Philip II of Spain became known. Wyatt later claimed to have been urged by Edward Courtenay, Earl of Devon, to join an uprising to prevent the marriage. Wyatt raised an army of four thousand in Kent, and marched on London in what became known as "Wyatt's rebellion". He was found guilty of treason and beheaded at the Tower of London. After he was beheaded, his body was dismembered.
Wyatt's rebellion was thought by many to have been raised with the intention of putting Princess Elizabeth on the throne in her sister's place, and almost cost the princess her life.