Among his most famous works are his Commentary on Plato’s Teachings on the Origin of the Soul, and the Chronographia, a series of biographies from emperor Basil II to Nikephoros III, which serves as a valuable source on the history of the 11th century Byzantine Empire.

At around the age of ten, he was sent to work outside the capital as a secretary of a provincial judge, to help his family raise the dowry for his sister.

He became an influential political advisor to emperor Constantine IX Monomachos (reigned 1042–1055) and became the leading professor at the University of Constantinople, bearing the honorary title of "Chief of the Philosophers" (ὕπατος τῶν φιλοσόφων hypatos tōn philosophōn).

Unlike most other historiographical works of the period, it emphasizes the description of characters rather than details of political and military events.

The second, which has a much more strongly apologetic tone, is in large parts an encomium on Psellus' protectors, the emperors of the Doukas dynasty.

Among modern commentators, Psellos' penchant for long autobiographical digressions in his works has earned him accusations of vanity and ambition.

However, other commentators argue that there is a powerful ironic undercurrent running through his work, especially the Chronographia, transmitting highly critical and subversive messages about the emperors portrayed,[14] or even about Byzantine Christian beliefs and morality at large.

For example, according to Byzantinist Anthony Kaldellis, "In 1054 he [Psellos] was accused by his erstwhile friend, the future Patriarch John Xiphilinos, of forsaking Christ to follow Plato.

[16] It was once thought that there was another Byzantine writer of the same name, Michael Psellos the Elder (now also called Pseudo-Psellos), who lived on the island of Andros in the 9th century, and who was a pupil of Photius and teacher of emperor Leo VI the Wise.

[17] The term "Pseudo-Psellos" is also used in modern scholarship to describe the authorship of several later works that are believed to have been falsely ascribed to Psellos in Byzantine times.

In the gloss of Samuel Taylor Coleridge's poem "The Rime of the Ancient Mariner", there is a reference to "the Platonic Constantinopolitan, Michael Psellus" as an authority on "the invisible inhabitants of this planet, neither departed souls nor angels".

The British poet Christopher Middleton includes a poem about Psellus in his 1986 collection, Two Horse Wagon Going By, "Mezzomephistophelean Scholion".