From the year following its inauguration, the Palazzo delle Esposizioni was the permanent site for over three decades for the exhibitions of the Società degli Amatori e Cultori di Belle Arti (Society for Fine Art Collectors and Connoisseurs), an association founded in 1829 and composed of the most representative artists working in Rome, together with leading figures among the ruling elite, the aristocracy, merchants, intellectuals and academics. It was a society that came into existence in the culturally conservative climate of the Papal city of Rome, and it was mainly focused on the Rome art scene, although it was also supported by figures such as Bertel Thorvaldsen and Horace Vernet, with King Ludwig of Bavaria elected as honorary president. The exhibitions reflected an extremely conservative vision, even by comparison with other centres of artistic culture in Italy, and thus Rome failed to take on the role of international showcase which was assumed a few years later by the Venice Biennial.
An attempt at modernization was made with the four International Exhibitions of Secession Art, which took place at the Palazzo delle Esposizioni from 1913 to 1916 with the aim of documenting what was happening abroad, though with a certain time lag, as well as the work of artists in Italy inspired by a general modernism, working in various fields from painting to sculpture, and from architecture to applied arts. The phenomenon of the profound renewal of taste, artistic conception and expressive forms that occurred in France, Germany, Austria and other European countries in the various Secession or Art Nouveau movements, did not really make itself felt in Rome.
In 1927, the Governatorato of Rome decided to institute the Esposizioni Quadriennali d’Arte Nazionale (Quadrennial Exhibitions of National Art), to be held in the Palazzo delle Esposizioni, with the first exhibition to be inaugurated on 1 March 1931. During their deliberations, in addition to the appointment of the members of the organizing committee presided over by the Governatore (representatives from the Accademia di San Luca, the Società degli Amatori e Cultori di Belle Arti, the international artistic association and artists appointed by various institutions), the budget was also established: 250,000 lire annually and one million lire for each staging of the exhibition. It was also decided to provide prizes and to set aside a substantial sum for the acquisition of works of art for the Galleria Nazionale. The first Quadrennial, under the direction of the general secretary, Cipriano Efisio Oppo, was inaugurated on 3 January 1931, which was actually earlier than anticipated. The works were selected by two juries of artists, one nominated by the organizing committee and the other by representatives of the exhibiting artists themselves. The first prizes were awarded to Arturo Tosi and Arturo Martini, with important retrospectives being dedicated to Medardo Rosso and Armando Spadini, and to Antonio Mancini who had just died.
In 1930, work began on the restructuring of the Palazzo delle Esposizioni to adapt its spaces to the exhibition’s requirements. As can be seen from the chronicles of this period and from the various sittings of the commission, it was necessary to enlarge the exhibition halls, install lifts, adapt the lighting, and provide a heating system to regulate the internal temperature which was too cold in winter and too hot in summer, and thus it was decided to knock down the "ugly and expensive railway station glass canopy". Architects Del Debbio and Aschieri were assigned this task: the former was responsible for the demolition of the glass canopy and the construction of a floor, in order to be able to obtain a further six exhibition rooms around a central hall on the floor below. Thus the architect followed the actual layout designed by Piacentini for the principal part of the building, though in a more limited way, reviving at the same time the mirror-like quality of the whole project. Aschieri (who was also responsible for mounting the second Quadrennial) set up the exhibition is such as way as to eliminate the monumental effect of the building, seeking a rational, sober and elegant sense of proportion, in which the works of art would have clear visibility and a clear background.
Commenting on the work on the building and on the mounting of the exhibition, architect Luigi Piccinato emphasized how Aschieri and Del Debbio had "restored life to the large halls of Via Nazionale. By proportioning rooms, arranging partitions, softening lighting, and reducing shadow, the vast array of paintings was organized and enhanced within a calm, simple, refined and restful setting. In the public spaces, that is the Vestibule, the Winter Garden, the stairs, and the corridors, where the neutral tone was no longer necessary, they were free to make architecture" (from the March 1931 edition of Domus magazine).The exhibition, which Mussolini termed "historic", received notable critical and public acclaim (with over 200,000 visitors) and the restoration work was widely appreciated, thus confirming the building’s definitive destination as the site of the Quadrennial.
One particularly significant episode in the activities of the exhibition during this period was the fascist revolution Exhibition, promoted by the national fascist party on the tenth anniversary of the march on Rome. The exhibition was inaugurated on 28 October 1932 and the preparation work was regularly submitted to the approval of the Duce, who defined it as the "sacred, impressive and solemn record" of the genesis, development and goals attained by fascism. Obviously, this exhibition was solely for propaganda and celebratory purposes, but it also represented a remarkable conception of an exhibition event. The catalogue states: "The monumental nature of this exhibition cannot but adopt a spectacular style of architecture, so to speak, designed to evoke the atmosphere of the times, all fire and fever, tumultuous, lyrical and brilliant." The words reveal a futurist climate that was undoubtedly reflected not only in many of the works of art on exhibit, but also in the layout of the exhibition, the result of a collaboration between artists (Nizzoli, Funi, Maccari, and especially Sironi) and architects (Terragni, Libera, and Valente), while the external facade, designed by De Renzi and Libera, in its formalism and in the explicitly ideological nature of the work (the 25 metre high metal "fasces") testified to a European-based architectural culture.
This exhibition was to have been moved to the Palazzo del Littorio for its permanent headquarters, but since this had not yet been built, it was kept at the Palazzo delle Esposizioni for a further two years, so that the second Quadriennale was organized to a very tight deadline and was inaugurated on 5 February 1935. Architects Aschieri and Montuori were responsible for mounting the exhibition; Piacentini’s facade was revealed once more, limited to a sober entrance door from the colonnaded porch. Inside, the facing of the central rotonda, the covering awnings, and the three gradations of grey on the display walls created a very striking, almost metaphysical, atmosphere, in which the 1,800 works of art were arranged, including paintings, sculptures and works in black and white. There were many personal exhibitions (including one dedicated to Scipione, who had died two years previously), with particular attention given to young artists and to different trends, from the late futurists to the abstractionists, who had their epicentre in Milan at the Galleria del Milione, and to more conservative trends. The Rome School of artists had an important presence, especially Mafai who had a room exhibiting 29 of his works and who was awarded a prize for his painting Lezione di piano (Piano Lessons).
In 1937, the Esposizione Nazionale Quadriennale d’Arte di Roma (Rome Quadrennial National Art Exhibition) was made an independent body by royal decree, with its own statute signed by the Minister for National Education, Giuseppe Bottai. The third exhibition, inaugurated on 5 February 1939, was therefore directly managed by the authority, under the supervision of the Minister of national education and the Minister for corporations, who, in compliance with the racial laws issued the previous year, required very strict inspection and documentation of the origins of each artist, with the compilation of individual files. It was a rather confused exhibition, compromised above all by very heavy political interference, reflecting what was anyway a situation of crisis in the artistic field. Architects Mario Paniconi and Giulio Pediconi were responsible for the mounting of the exhibition, taking particular care over the details, increasing the number of rooms and focusing especially on the clear visibility of the works of art, and on the restraint and general dignity of the environments. The exhibition of works by Giorgio Morandi and the section dedicated to paintings and futurist sculptures of aircraft are worthy of note. The fourth Quadriennale opened in May 1943, in the middle of the war, and was the last under the direction of Cipriano Efisio Oppo. It was a greatly reduced exhibition (only some of the rooms were used), mounted by architect Ernesto Puppo and by engineer Alessandro Mangioni. The most significant aspects were the works by Enrico Prampolini and the futurist painters. The main prizes were awarded to Vagnetti and Manzù. At the end of the war, the Palazzo delle Esposizioni was occupied by food-rationing offices and the Ente Autonomo Quadriennale (Independent Quadrennial Authority) was placed under an administrator.