Born in Eisenach in the Thuringian Duchy of Saxe-Weimar-Eisenach, Wislicenus studied at the Dresden Academy of Fine Arts and later became a student of Eduard Bendemann and Julius Schnorr.
A stipend from the Grand Duke of Weimar enabled him to study in Italy (1853–1857) where he lived in Rome and became a follower of Peter von Cornelius and the Nazarene movement.
In an 1877 competition for the decoration of the restored Goslar Kaiserpfalz, he won the first prize, and, assisted by some of his pupils, within twenty years completed a series of 68 frescoes postulating a continuity of imperial rule from Charlemagne to the Prussian-led German Empire.
Wislicenus's pictorial agenda became an icon of the Romantic recourse to medieval traditions that served the inner identity of the 'Lesser German' Reich established in 1871.
Among other oil paintings, watercolors, and cartoons, he executed "Night With Its Retinue," for the Grand Duke of Weimar, the "Myth of Prometheus" (1862, Leipzig Museum), "The Flood of Deucalion" (1865, Weimar Museum); the mural paintings "Brutus as Judge of his Sons" and "The Mother of the Gracchi," in the staircase of the Härtel Roman House at Leipzig; "Fancy Borne by the Dreams" (Schaek Gallery, Munich); "Angels Singing Psalms," mural painting (Grand-ducal chapel, Weimar).