Niccolo was the assistant of his father Giovanni and completed his studies with Antonio Begarelli, a sculptor. Much influence by Corregio, he was first a soldier but soon gave up his military career to dedicate himself to painting. In 1537, he worked with Alberto Fontana to decorate the butchers' house in Modena and later in the town palace where he painted mythological scenes.
The frescoes he painted in the castle of Scondiano established his reputation and are now shown in the museum of Modena. In 1547 he painted an altar piece for the church of St Peter, which also earned him fame and then went on to work in Bologna where his frescoes in the Torfanini palace, however now lost, much impressed the Carracci brothers. He also executed frescoes in the Poggi palace representing young men and women painted with much grace and produced another fresco showing the nativity under the porch of the Leoni Palace.
Niccolo was then summoned to the French court by King Henri II on the advice of Primaticcio in 1552 and painted the portraits of the latter and his wife. He then settled in Fontainebleau with his wife and three sons, Giulio, Christoforo and Camillo.
During his 19-year stay in France, he produced many important works while helping Primaticcio in Fontainebleau. He notably painted eight large paintings for the St Louis room, decorated the ballroom and executed a series of works after the Odyssey in the Ulysses gallery, which was alas destroyed in 1738.
In the Alexandre room, replaced by a stairway under King Louis 15th, Niccolo painted in 1570 frescoes of which eight have survived. He also decorated in 1561 the dairy-farm, the Meudon pavilion, destroyed under Louis 14th, the chapel of the Guise Mansion-house, the Hôtel de Toulouse, the Hôtel de Montmorency and the Château de beauregard near Blois. All these paintings were later destroyed notably some erotic works, regarded as pagan themes, which were burnt on the order of the Regent queen Anne of Austria in 1643.
Many important paintings by Niccolo dell Abbate thus were committed to the flames causing an irreparable art loss while vandals destroyed Michelangelo's Leda and the Swan in Florence when that city was besieged.
Niccolo was also an excellent landscape painter and executed many genre paintings according to the French royal inventory list. Enjoying a great reputation, he also decorated the arks of triumph erected in Paris for the entry of Charles 9th in the French capital in March 1571. During the second day of that event he painted 16 works in the great room of the Paris Diocese with the help of his son Giulio, a few weeks before his death in Fontainebleau.