He studied painting at the School of the Arts (1850-1856), taught by the Phillippo brothers and Georgios Margaritis, Agathangelos Triantafyllou, Raffaello Ceccoli and Ludwig Thiersch, whom he helped decorate the Russian Church in Athens (1853-1855). In 1860, after having taught Introductory Illustrating for two years at the School of the Arts (1856-1858), he went to Munich, where, initially thanks to a scholarship by the Greek state and then to the support of Baron Simon Sinas, he completed his studies at the Academy of Fine Arts, with Karl von Piloty as his principal instructor. In 1865, he returned to Athens and the following year he was appointed Professor of Painting at the National Technical University, a position which he retained until his death. He was close friends with Nikolaos Gyzis, whom he escorted on his trip to Asia Minor in 1873, Munich in 1874 (where Lytras stayed until 1875) and Paris in 1876, while in 1879 he travelled to Egypt.
In 1855, while still a student, he took part in the Paris World Fair, in which he also participated in 1867, 1878, 1889 and 1900, winning a bronze medal in the last two occasions, while in 1873 he took part in the World Exhibition in Vienna. In addition, he was also very active in Greece, participating in the exhibition of the House of Melas in 1881, the Panhellenic Exhibition at Zappeion in 1888, the Panhellenic Exhibition organized in the context of the first modern-day Olympic Games in 1896, in several exhibitions of the Parnassos cultural society, etc. After his death, works of his were presented in various events in Greece and abroad, such as the exhibition “The School of Piloty 1858-1886” held in 1909 at the Heinemann Gallery in Munich and the International Fair of Rome in 1911. In addition, the School of Fine Arts organized a large-scale retrospective of his work in 1933.
Nikiforos Lytras was one of the main representatives of the Munich School and is considered the father of modern Greek painting. Although acquainted with impressionism, he stayed true to the academic tradition and was active in almost all subject areas: portraits, still lifes, historical scenes and mythological themes. Yet, the most important part of his work were genre scenes, which he essentially introduced into Greek painting. These include scenes from both the Greek countryside and urban setting, the Greek family and the world of the children, as well as themes from the Orient. He is also considered an innovator in the field of portraits, in which he displays a patent attempt to delve into the personality of his subject. Also a very important part of his contribution was his forty-year-long teaching tenure at the School of Fine Arts, throughout which he constantly strived to upgrade the level of studies and promote the reorganization of the artistic department, and which exercised a profound influence on future generations of artists.