Barthélemy d’Eyck probably began his career as early as 1435. He was related to Jan van Eyck and worked in his Bruges workshop as an illuminator.

A triptych with a representation of the Annunciation, which was produced in 1442–1445 on the commission of the draper Pierre Corpici for the cathedral of Aix-en-Provence, can be reliably attributed to Barthélemy d’Eyck who was provably there in 1445. It is the key work in the discussion concerning the early influence of northern painting on the south and exhibits the influence of Campin and Van Eyck.

After rendering service to the Prince Bishop of Liège, Barthélemy d’Eyck worked at the court of René of Anjou from 1447 to 1470. He also painted the miniatures for the novel Coeur d´amour épris written by the king in 1457 (Vienna, Austrian National Library, Ms. 2597).