In 1804 Wilkie returned to Cults, established himself in the manse, and began his first important subject-picture, Pitlessie Fair, which includes about 140 figures, and in which he introduced portraits of his neighbours and of several members of his family circle. In addition to this elaborate figure-piece, Wilkie was much employed at the time upon portraits, both at home and in Kinghorn, St Andrews and Aberdeen. In the spring of 1805 he left Scotland for London, carrying with him his Bounty-Money, or the Village Recruit, which he soon disposed of for £6, and began to study in the schools of the Royal Academy. One of his first patrons in London was Stodart, a pianoforte maker, a distant connection of the Wilkie family, who commissioned his portrait and other works and introduced the young artist to the dowager-countess of Mansfield. This lady's son was the purchaser of the Village Politicians, which attracted great attention when it was exhibited in the Royal Academy of 1806, where it was followed in the succeeding year by the Blind Fiddler, a commission from the painter's lifelong friend Sir George Beaumont.
Wilkie now turned aside into the paths of historical art, and painted his Alfred in the Neatherd's Cottage, for the gallery illustrative of English history which was being formed by Alexander Davison. After its completion he returned to genre-painting, producing the Card-Players and the admirable picture of the Rent Day which was composed during recovery from a fever contracted in 1807 while on a visit to his native village. His next great work was the Ale-House Door, afterwards entitled The Village Festival (now in the National Gallery), which was purchased by John Julius Angerstein for 800 guineas. It was followed in 1813 by the well-known Blind Man's Buff, a commission from the Prince Regent, to which a companion picture, the Penny Wedding, was added in 1818.
Meanwhile, Wilkie's eminent success in art had been rewarded by professional honours. In November 1809 he was elected an associate of the Royal Academy, when he had hardly attained the age prescribed by its laws, and in February 1811 he became a full Academician. In 1812 he opened an exhibition of his collected works in Pall Mall, but the experiment was unsuccessful, entailing pecuniary loss upon the artist.
In 1814 he executed the Letter of Introduction, one of the most delicately finished and perfect of his cabinet pictures. In the same year he made his first visit to the continent, and in Paris entered upon a profitable and delighted study of the works of art collected in the Louvre. Interesting particulars of the time are preserved in his own matter-of-fact diary, and in the more sprightly and flowing pages of the journal of Benjamin Haydon, his fellow traveller. On his return he began Distraining for Rent, one of the most popular and dramatic of his works. In 1816 he made a tour through Holland and Belgium in company with Raimbach, the engraver of many of his paintings. The Sir Walter Scott and his Family, a cabinet-sized picture with small full-length figures in the dress of Scottish peasants, was the result of a visit to Abbotsford in 1818. Reading a Will, a commission from the king of Bavaria, now in the New Pinakothek at Munich, was completed in 1820; and two years later the great picture of Chelsea Pensioners Reading the Gazette of the Battle of Waterloo, commissioned by the Duke of Wellington in 1816, at a cost of 1200 guineas, was exhibited at the Royal Academy.
In 1822 Wilkie visited Edinburgh, in order to select from the Visit of King George IV to Scotland a fitting subject for a picture. The Reception of the King at the Entrance of Holyrood Palace was the incident ultimately chosen; and in the following year, when the artist, upon the death of Raeburn, had been appointed Royal Limner for Scotland, he received sittings from the monarch, and began to work diligently upon the subject. But several years elapsed before its completion; for, like all such ceremonial works, it proved a harassing commission, uncongenial to the painter while in progress and unsatisfactory when finished. His health suffered from the strain to which he was subjected, and his condition was aggravated by heavy domestic trials and responsibilities.
In 1825 he sought relief in foreign travel: after visiting Paris, he went to Italy, where, in Rome, he received the news of fresh disasters through the failure of his publishers. A residence at Toplitz and Carlsbad was tried in 1826, with little good result, and then Wilkie returned to Italy, to Venice and Florence. The summer of 1827 was spent in Geneva, where he had sufficiently recovered to paint his Princess Doria Washing the Pilgrims' Feet, a work which, like several small pictures executed in Rome, was strongly influenced by the Italian art by which the painter had been surrounded. In October he passed into Spain, whence he returned to England in June 1828.
It is impossible to over-estimate the influence upon Wilkie's art of these three years of foreign travel. It amounts to nothing short of a complete change of style. Up to the period of his leaving England he had been mainly influenced by the Dutch genre-painters, whose technique he had carefully studied, whose works he frequently kept beside him in his studio for reference as he painted, and whose method he applied to the rendering of those scenes of English and Scottish life of which he was so close and faithful an observer. Teniers, in particular, appears to have been his chief master; and in his earlier productions we find the sharp, precise, spirited touch, the rather subdued colouring, and the clear, silvery grey tone which distinguish this master; while in his subjects of a slightly later period--those, such as the Chelsea Pensioners, the Highland Whisky Still and the Rabbit on the Wall, executed in what Burnet styles his second manner, which, however, may be regarded as only the development and maturity of his first--he begins to unite to the qualities of Teniers that greater richness and fulness of effect which are characteristic of Ostade. But now he experienced the spell of the Italian masters, and of Diego Velázquez and the great Spaniards.
In the beginning of 1830 Wilkie was appointed to succeed Sir T Lawrence as painter in ordinary to the king, and in 1836 he received the honour of knighthood. The main figure-pictures which occupied him until the end were "Columbus in the Convent at La Rabida" (1835); "Napoleon and Pius VII. at Fontainebleau" (1836); "Sir David Baird Discovering the Body of Tippoo Sahib" (1838); the "Empress Josephine and the Fortune-Teller" (1838); and "Queen Victoria Presiding at her First Council" (1838). His time was also much occupied with portraiture, many of his works of this class being royal commissions. His portraits are pictorial and excellent in general distribution, but the faces are frequently wanting in drawing and character. He seldom succeeded in showing his sitters at their best, and his female portraits, in particular, rarely gave satisfaction. A favourable example of his cabinet-sized portraits is that of Sir Robert Listen; his likeness of W. Esdaile is an admirable three-quarter length; and one of his finest full-lengths is the gallery portrait of Lord Kellie, in the town hall of Cupar.
In the autumn of 1840 Wilkie resolved on a voyage to the East. Passing through Holland and Germany, he reached Constantinople, where, while detained by the war in Syria, he painted a portrait of the young sultan. He then sailed for Smyrna and travelled to Jerusalem, where he remained for some five busy weeks. The last work of all upon which he was engaged was a portrait of Mehemet Ali, done at Alexandria. On his return voyage he suffered from an attack of illness at Malta, and died at sea off Gibraltar on the morning of the 1st of June 1841. His body was consigned to the deep in the Bay of Gibraltar.