After spending his early childhood in Tinos, in 1850 he settled with his father in Athens, in order to be able to systematically cultivate his aptitude for painting. Due to his young age, he audited, without officially enrolling, courses at the National Technical University. He finally enrolled in 1854 and studied there until 1864 under teachers such as Filippos Margaritis, Agathangelos Triantafyllou, Raffaello Ceccoli, Ludwig Thiersch, Petros Pavlidis-Minotos and Vasileios Karoubas-Skopas. In 1859, he took part in the Olympia exhibition. In 1862, on referral from his fellow islander and close friend Nikiforos Lytras, he met with Nikolaos Nazos, also from Tinos island, who was later to become his father-in-law, and who helped Gyzis reveice a scholarship from the Foundation of the Evangelistria of Tinos. In mid-1865 he left for Munich, where he studied under Hermann Anschütz and Alexander von Wagner at the Academy of Fine Arts, before being accepted, in 1868, to the class of Karl von Piloty. In Munich he was introduced to the art scene by Lytras, who had already been established there since 1860. Before long, Gyzis got accepted into the Leibl Circle, while he also became friends with painters Franz von Defregger, Eduard Kurzbauer and, later, Franz von Lenbach. After participating in exhibitions in Munich and Vienna, he left in 1872 to go to Greece, where he remained for two years. The journey to the Orient, which he took in 1873 escorted by Lytras, had a profound influence on his perception and rendering of color and light in his work. He finally returned to Munich, for good this time, in 1874, thereafter regularly participating in the annual and international exhibitions of the Glaspalast. In 1875 he became a member of the artistic association “Αllotria”. At the Paris World Fair of 1878, where he participated in the German department, he won third prize and, in 1879, he served as a member of the jury at the International Exhibition in Munich. During 1878-1880 he painted the ceiling mural at the Museum of Decorative Arts in Kaiserslautern. In 1880 he became an honorary member of the Academy of Fine Arts, in 1882 an associate professor at the Munich Academy of Fine Arts and six years later, in 1888, a tenured professor. In addition to genre painting, still lifes and portraits, by the mid-1880s Gyzis had turned to idealistic-allegorical themes, which he had begun to approach as early as the mid-1870s. Thus, he would emerge as the voice of a new spirit, which was then being cultivated in Munich, as a forerunner to Jugendstil. In 1887 he designed the flag of the National and Kapodistrian University of Athens and, a year later, he created the “Spirit of Art” for the 3rd International Exhibition of Munich, which marked his turn toward the artistic poster. In 1892 he won gold medals at the International Exhibition in Munich and Madrid and was elected member of the jury for the 1893 International Exhibition of Chicago. That year he also illustrated the short story “Philippos Marthas” by Dimitrios Vikelas. In 1895 he took his last trip to Greece. In 1896 he completed the Diploma for the Olympic Games, while in the years 1895-1899 he created the great idealistic composition “The Apotheosis of Bavaria” for the Museum of Decorative Arts in Nuremberg. In 1899 he sent his work “Glory” to the exhibition of Athens. In 1900 his works “New Century” and “Spring Symphony” were presented at the Paris World Fair and the Glaspalast featured his large-scale composition “Behold, the Bridegroom”, a work that is part of his religious visions, which the artist did not have the time to complete. In 1901 the Glaspalast hosted a posthumous exhibition dedicated to the recently departed artists Wilhelm Leibl, Arnold Bocklin and Nikolaos Gyzis. One year later, Marcel Montandon published the artist's biography. In 1928, the Society of Art Devotees organized a retrospective at the Iliou Melathron containing four hundred and sixty-three of his works. In 2001, the National Gallery of Athens presented a major retrospective exhibition of his work on the occasion of the centenary of his death.
A dominant figure of the Munich School, Gyzis influenced the course of Greek art through his painting, while he also holds a prominent position in the history of 19th-century German art. In his genre paintings he managed to transcend the level of mere narration, while his full caliber is best illustrated in his idealistic, allegorical and religious work, i.e. themes in which he was in step with the quests of the avant-garde Jugendstil movement.