Wyatt was over six feet tall, reportedly both handsome and physically strong. Wyatt was not only a poet, but also an ambassador in the service of Henry VIII. He first entered Henry's service in 1516 as 'Sewer Extraordinary', and the same year he began studying at St John's College of the University of Cambridge. He married Elizabeth Brooke (1503–1560), the sister of George Brooke, 9th Baron Cobham, in 1521, and a year later she gave birth to a son, Thomas Wyatt, the younger, who led Wyatt's rebellion many years after his father's death. In 1524 Henry VIII assigned Wyatt to be an Ambassador at home and abroad, and some time soon after he separated from his wife on the grounds of adultery.

He accompanied Sir John Russell to Rome to help petition Pope Clement VII to annul the marriage of Henry VIII to his first wife, Catherine of Aragon, an embassy whose goal was to make Henry free to marry Anne Boleyn. According to some, Wyatt was captured by the armies of Emperor Charles V when they captured Rome and imprisoned the Pope in 1527 but managed to escape and then made it back to England. In 1535 Wyatt was knighted.

Wyatt's professed object was to experiment with the English tongue,to civilise it,to raise its powers to those of its neighbours. and although a significant amount of his literary output consists of translations of sonnets by the Italian poet Petrarch, he wrote sonnets of his own. Wyatt's sonnets first appeared in Tottle's Miscellany, now on exhibit in the British Library in London. In addition to imitations of works by the classical writers Seneca and Horace, he experimented in stanza forms including the rondeau, epigrams, terza rima, ottava rima songs , satires and also with monorime,triplets with refrains,quatrains with different length of line and rhyme schemei ,quatrains with codas, and the French forms of douzaine and treizaine in addition to introducing contemporaries to his poulter's measure form (Alexandrine couplets of twelve syllable iambic lines alternating with a fourteener,fourteen syllable line). and is acknowledged a master in the iambic tetrameter .While Wyatt's poetry reflects classical and Italian models, he also admired the work of Chaucer and his vocabulary reflects Chaucer’s (for example, his use of Chaucer’s word newfangleness, meaning fickle, in They flee from me that sometime did me seek). His best-known poems are those that deal with the trials of romantic love. Others of his poems were scathing, satirical indictments of the hypocrisies and flat-out pandering required of courtiers ambitious to advance at the Tudor court.

The Egerton Manuscript, originally an album containing Wyatt's personal selection of his poems and translations, preserves 123 texts, partly in the poet's hand.Tottel's Miscellany (1557), the Elizabethan anthology which created Wyatt's posthumous reputation, ascribes 96 poems to him,(33 not extant in the Egerton Manuscript).Another 129 poems derive mostly from two Tudor manuscript anthologies, the Devonshire and Blage manuscripts .R A Rebbholz in his preface to Sir Thomas Wyatt,The Complete Poems comments 'the problem of determining which poems Wyatt wrote is as yet unsolved'. However, Richard Harrier's The Canon of Sir Thomas Wyatt's Poetry (1975) examines the textual evidence and establishes that there is insufficient textual warrant for assigning any of these poems to Wyatt.  Ultimately, their inclusion rests on arbitrary editorial judgment.The only basis for ascribing these poems to Wyatt resides in editorial evaluation of their style and poetic merits.  Compared with the indubitable standard of Wyatt's 156 unquestionably ascribable poems, fewer than 30 survive scrutiny.  The best edition of Wyatt thus far is Joost Daalder's (1975).  It presents 199 poems, including 25 misascriptions (mostly segregated as "Unascribed") and is missing a dozen poems likely to be Wyatt's.  A proper edition of this major poet, the inventor of lyric poetry in Modern English, is urgently needed.

Critical opinions of his work have varied widely..Warton,the eighteenth century critic,considered Wyatt 'confessedly an inferior' to his contemporary Henry Howard, Earl of Surrey and that Wyatt's ' genius was of the moral and didatic species and be deemed the first polished English satirist '.. The 20th century saw an awakening in his popularity and a surge in critical attention. C. S. Lewis called him ‘the father of the Drab Age’,(i.e. the unornate,from what Lewis calls the 'golden' age of the 16th century ,while others see his love poetry, with its complex use of literary conceits, as anticipating that of the metaphysical poets in the next century.More recently, the critic, Patricia Thomson, describes Wyatt as the Father of English Poetry

Many legends and conjectures have grown up around the notion that the young, unhappily married Wyatt fell in love with the young Anne Boleyn in the early-to-mid 1520s. His grandson (who penned a biography of Anne Boleyn many years after her death) wrote that the moment Thomas Wyatt had seen "this new beauty" on her return from France in winter 1522 he had fallen in love with her. According to various gossips they were lovers. Allegedly Wyatt was Anne's suitor, even though he was married. When she attracted King Henry VIII's attentions sometime around 1525, Wyatt was the last of Anne's other suitors to be ousted by the king. According to Wyatt's grandson, after an argument over her during a game of bowls with the King, Wyatt was sent on, or himself requested, a diplomatic mission to Italy.

Wyatt's translation from Petrarch, "Whoso list to hunt," may refer to his early encounter with Anne Boleyn. Wyatt was at Calais when she and King Henry made their only foreign sojourn together (only a short time before they were married in secret). His poem "Sometime I fled the fire" may refer to this voyage. In January 1533, Anne Boleyn is said to have told Wyatt, in front of other courtiers, that she had a 'hankering for apples' and that the King thought she might be pregnant. This was how the court discovered that Henry and Anne were already married. Wyatt was also Chief Ewer (a distinguished serving role) at her Coronation. One poem of Wyatt's that certainly refers to Boleyn, after her demise, is "After great storms the calm returns;" its refrain, "the most happy," was one of her official mottoes.

In May 1536 Wyatt was imprisoned in the Tower of London for allegedly committing adultery with Anne Boleyn. He was released from the Tower later that year, thanks to his friendship or his father's friendship with Thomas Cromwell, and he returned to his duties. During his stay in the Tower he may have witnessed not only the execution of Anne Boleyn (May 19, 1536) from his cell window but also the prior executions of the five men with whom she was accused of adultery. Wyatt is known to have written a poem inspired by the experience (http://www.luminarium.org/renlit/innocent.htm), which, though it stays clear of declaring the executions groundless, expresses grief and shock.

In the 1530s, he wrote poetry in the Devonshire MS declaring his love for a woman; employing the basic acrostic formula, the first letter of each line spells out SHELTUN. A reply is written underneath it, signed by Mary Shelton, rejecting him. Mary, Anne Boleyn's first cousin, had been the mistress of Henry VIII between February and August 1535.

In 1540 he was again in favor, as evident by the fact that he was granted the site and many of the manorial estates of the dissolved Boxley Abbey. However, in 1541 he was charged again with treason and the charges were again lifted...though only thanks to the intervention of Henry's fifth wife, then-Queen Catherine Howard, and upon the condition of reconciling with his adulterous wife. He was granted a full pardon and restored once again to his duties as ambassador. After the execution of Catherine Howard, there were rumours that Wyatt's wife, Elizabeth, was a possibility for wife number six, despite the fact that she was still married to Wyatt. He became ill not long after, and died on 11 October 1542 around the age of 39, while staying with his friend Sir John Horsey at Clifton Maybank House in Dorset. He is buried in nearby Sherborne Abbey.

Long after Thomas Wyatt's death, his only son, Thomas Wyatt the younger, led a thwarted rebellion against Henry's daughter, Queen Mary I, for which he was executed. The rebellion's aim was to set the Protestant-minded Elizabeth, the daughter of Anne Boleyn, on the throne. His sister Margaret Wyatt was the mother of Henry Lee of Ditchley, from whom descend the Lee's of Virginia, including Robert E. Lee. Thomas Wyatt's great grandson was Virginia Governor Francis Wyatt.