[1] Wyatt spent six years in Italy, 1762–68, in company with Richard Bagot of Staffordshire, who was Secretary to Charles Compton, 7th Earl of Northampton's embassy to the Venetian Republic.

In Rome he made measured drawings of the dome of St. Peter's Basilica, "being under the necessity of lying on his back on a ladder slung horizontally, without cradle or side-rail, over a frightful void of 300 feet".

[2] His polished manners secured him friends as well as patrons among the great, and when it was rumoured that he was about to leave the country to become architect to Catherine II of Russia, a group of English noblemen is said to have offered him a retaining fee of £1,200 to remain in their service.

In about 1800, he was commissioned to carry out alterations to Windsor Castle which would probably have been much more considerable had it not been for George III's illness, and in 1802 he designed for the King the "strange castellated palace" at Kew which was remarkable for the extensive employment of cast iron in its construction.

As early as 1790, when he was invited to submit designs for rebuilding St Chad's Church at Shrewsbury, he broke his engagements with such frequency that the committee "became at length offended, and addressed themselves to Mr. George Stewart".

His conduct of official business was no better than his treatment of his private clients, and there can be no doubt that it was Wyatt's irresponsible habits which led to the reorganization of the Board of Works after his death, as a result of which the Surveyor's office was placed in the hands of a political chief assisted by three "attached architects".

At the time he began practice the fashionable architects were the brothers Adam, whose style of interior decoration he proceeded to imitate with such success that they complained of plagiarism in the introduction to their Works in Architecture, which appeared in 1773.

Many years later Wyatt himself told George III that "there had been no regular architecture since Sir William Chambers – that when he came from Italy he found the public taste corrupted by the Adams, and he was obliged to comply with it".

Much of Wyatt's classical work is, in fact, in a chastened Adam manner with ornaments in Coade stone and Etruscan-style medallions executed in many cases by the painter Biagio Rebecca, who was also employed by his rivals.

It was not until towards the end of his life that he and his brother Samuel (with whom must be associated their nephew Lewis) developed the severe and fastidious style of domestic architecture which is characteristic of the Wyatt manner at its best.

[a] But among Wyatt's earlier works there are several (e.g., the Christ Church gateway and the mausoleum at Cobham) which show a familiarity with Chambers' Treatise on the Decorative Part of Civil Architecture.

Had he been given the opportunity of designing some great public building, it is possible that he would have shown himself a true disciple of Chambers;[b] but his career as a government architect coincided with the Napoleonic wars, and his premature death deprived him of participation in the metropolitan improvements of the reign of George IV.

In 1803 he was one of the members of the Council which attempted to assert its independence of the General Assembly of Academicians, and when the resultant dissensions led Benjamin West to resign the Presidency in the following year, it was Wyatt who was elected to take his place.