Ducreux specialized in portrait painting, and his early portraits were done in pastel, and include those done of the connoisseurs Pierre-Jean Mariette, the Comte de Caylus and Ange-Laurent de la Live de July. These works may have been copies after De La Tour.
Ducreux also made several well-known self-portraits in the late 1780s, including one in which he painted himself in the middle of a large yawn (which currently hangs in the Getty Center) and another of himself guffawing and pointing at the viewer (which hangs in the Louvre). As evidenced by these self-portraits, Ducreux attempted to break free from the constraints of traditional portraiture. Interested in physiognomy, which is based on the belief that the study and judgment of a person's outer appearance, primarily the face, reflects their character or personality, Ducreux attempted to capture the personality of his subjects - as well as his own - through his warm and individualistic works. Le Discret (ca. 1790), for example, is the portrait of a man asking for silence. His expression is timorous, his finger is pressed against his mouth in alarm as he silently demands discretion or prudence.
In 1769, he was sent to Vienna in order to paint a miniature of Marie-Antoinette before she left the city in 1770 and married Louis XVI of France. Ducreux was made a baron and premier peintre de la reine (First Painter to the Queen) in rewards for his services. Ducreux was given this appointment by Marie-Antoinette even though he was not a member of the Royal Academy of Painting and Sculpture.
Recently, Ducreux and his work have gone through a cultural renaissance as a result of his eccentric self-portrait being extensively used in an internet meme, featuring “archaic reinterpretation” of popular rap lyrics superimposed over the artwork. This highly verbose joke provides the challenge of “decoding” the corrupted lyrics back into to the original verses.