Mengs was born in 1728 at Ústí nad Labem (German: Aussig) in Bohemia, the son of
Ismael Mengs , a Danish painter who eventually established himself at Dresden. His elder sister, Therese Maron was also a painter, as was their younger sister Julia. In 1741 Mengs's father took him from Dresden to Rome.
In 1749 he was appointed first painter to Frederick Augustus, elector of Saxony, but this did not prevent him from continuing to spend much of his time in Rome. There he married Margarita Guazzi, who had sat for him as a model in 1748. He converted to Catholicism, and in 1754 he became director of the Vatican school of painting. His fresco painting of Parnassus at Villa Albani gained him a reputation as a master painter.
In 1749 Mengs accepted a commission from the Duke of Northumberland to make a copy, in oil on canvas, of Raphael's fresco The School of Athens for his London home. Executed in 1752–5, Mengs' painting is full-sized, but adapts the composition to a rectangular format, with some additional figures. It is now in the collection of the Victoria and Albert Museum. Mengs died in Rome in June 1779 and was buried in the Roman Church of Santi Michele e Magno.