The foundation of the Maronite College of Rome is rooted in the Roman Church's universal ambitions, first articulated at the Council of Ferrara-Florence, an ecumenical council held between 1431 and 1449. In continuation of these aspirations, and building on the doctrines established by the Council of Trent (1545–1563)—which mandated the creation of diocesan seminaries and colleges—several national colleges were inaugurated in Rome. Among these, the first was the Collegio Germanico-Ungarico (the Germanic-Hungarian College), founded in 1552 by Cardinal Giovanni Morone and St. Ignatius of Loyola. 

Subsequently, other institutions followed, including the Collegio Pontificio Greco (the Greek Pontifical College) in 1577 and the Collegio Polacco (the Polish College) in 1583. Most notably, the Collegio dei Maroniti (the Maronite College) was established by Pope Gregory XIII in 1584. This pattern continued with the founding of the Collegio Scozzese (the Scots College) in 1600 and the Collegio Irlandese (the Irish College of Rome) in 1625 (Benigni, 1912).

The Maronite College was instituted by the papal bull "Humana Sic Ferunt," issued on July 28, 1584, during the patriarchate of Maronite Patriarch Sarkis el-Rizzi (1581–1597). Initially managed by the Jesuits until 1773, it was then overseen by secular priests until the Napoleonic Wars, during which Rome was invaded, and the College was closed in 1803. Subsequently, its work was carried on by the College of Propaganda until Pope Leo XIII restored it in 1890 (Salibi, 1959). Cardinal Antonio Carafa, known as ‘the Cardinal Protector of the Maronites,’ assumed a significant role in the College's establishment, writing its first constitution in 1584 and bequeathing all his possessions to benefit the institution (Girard & Pizzorusso, 2017; Dib, 1971).

The primary aim of these colleges was to educate ecclesiastics and foster a strong allegiance to the Holy See (Benigni, 1912). Through their alumni, the Holy See sought to extend its jurisdiction by promoting Catholic principles in the vernacular languages of the target populations (Girard, 2017). Specifically, the Collegio dei Maroniti aimed to educate young Maronites from the ancient Patriarchate of Antioch, who lived under Islamic rule, so they could return to serve their native communities (Girard & Pizzorusso, 2017).

At the Maronite College, students received formation in the oriental rite and engaged in studies of Syriac and Arabic. Meanwhile, their studies of Latin and Italian and their education in spirituality, intellectual training, and various academic subjects were conducted mainly at the Collegio Romano. Founded in 1551 by St. Ignatius Loyola, the Collegio Romano later evolved into the Roman College, awarding academic degrees by 1556 (de la Croix & Karioun, 2021). Broggio (2002) stated that “the Collegio Romano was conceived as the common homeland for all the young foreigners residing in the Germanic College, the English College, the Maronite College, the Greek College, and so on, since they all attended its classes.

The education received at the Maronite College significantly influenced its alumni in their mission to spread education and intellectual growth in Lebanon and the surrounding regions. Moreover, they drove liturgical reforms in the Levant and worked to bring other non-uniate churches into the flock of the Roman Pontiff. Additionally, its alumni emerged as cultural, spiritual, intellectual, and diplomatic envoys, raising awareness in Europe about the plight and heritage of Eastern Christians and introducing European intellectual productions to the East.

Notably, the Maronite College served as fertile ground for cultivating virtuous ecclesiastics and scholars. Among its most distinguished alumni in the 16th and 17th centuries were Isaac Sciadrensis (Isḥāq al-Shidrawī), Ioannes Hesronita (Yūḥannā al-Ḥaṣrūnī), Gabriel Sionita (Jibrāʾīl al-Ṣahyūnī al-Iḥdīnī), Joannes Baptista Hesronita (Yūḥannā al-Ma'madān al-Ḥaṣrūnī), Sergius Risius (Sarkīs al-Rizzī), Michael Hesronita (Mīkhā’īl al-Ḥaṣrūnī), Vittorius Scialac (Naṣrallāh Shalaq al-ʿĀqūrī), Georgius Amira (Girgis 'Amīrah), Sergius Gamerius (Sarkīs al-Jamrī), Stephanus Edenensis (Isṭifān al-Duwayhī al-Iḥdīnī), Abraham Ecchellensis (Ibrāhīm al-Ḥāqilānī), Faustus Naironus (Murḥij Namrūn al-Bānī), Petrus Metoscita (Buṭrus al-Mtūshī), and Petrus Tulensis (Buṭrus al-Tūlāwī). In the 18th century, members of the Assemani (Assemānī) family exerted an indispensable role in the cultural landscape of the Vatican, Italian cities, and other major European cities. Collectively, these alumni were renowned for their polyglot abilities, extensive knowledge, and deep virtue.

The Maronite College fulfilled its mission by producing ecclesiastics dedicated to its founding purposes. It provided the Maronite Church and the Holy See with distinguished patriarchs, bishops, and priests who contributed significantly to their church, other Eastern Churches, Arab culture, and Lebanon's intellectual, cultural, and intercultural progress. Indeed, the Maronite College had the highest success rates among all the colleges. Broggio (2002) declared that “the most successful outcome [among the various established colleges] was the Maronite College, established with a Bull in 1584. Gregory XIII's successor, Pope Sixtus V Peretti, allocated significant revenues to it, which were later confirmed by Popes Paul V, Gregory XV, and Urban VIII.”

Furthermore, alumni of the College played a central role for both the Maronite community and the Universal Catholic Church, serving as a bridge between the Muslim East and the Christian West through activities such as translation, library and material culture curation, and diplomacy. Over the course of two centuries, Maronite orientalists and alumni significantly contributed to the development of oriental studies scholarship in Western Europe (Rietbergen, 1989). For the Maronites, the College provided essential education and a means to preserve their heritage while engaging with Western Christianity. For the Universal Catholic Church, it was a key institution, fostering the integration of Eastern Christian communities into the broader ecclesiastical framework and promoting unity and intellectual exchange.