On 1 June 1867, Comboni decided to open a training center which conducted seminars for clerics in Verona to be used in African missions: as a reference model for the organisation of the community, the Paris Foreign Missions Society was chosen as a company of priests and lay brothers, without religious vows, but with an oath of loyalty and belonging to the community. The leadership and teaching in the institute were entrusted to the Jesuit. 
The missionary society, originally called the children of the Sacred Heart of Jesus, was approved as a congregation of diocesan right on 8 December 1871. 
On 31 July 1877, Comboni was named apostolic Vicar of Central Africa and moved to Khartoum, where he died in 1881. With the founder's death, his company entered a phase of precariousness: the Mahdist War prevented missionaries from continuing their mission to Sudan. 
Francesco Sogaro, Comboni's first successor, transformed the society into a congregation of simple vows in 1885, but older members did not accept the decision because they believed that religious practices would distract the missionaries from the active apostolate. Only the decision of the Sacred Congregation for the Propagation of the Faith, which approved Sogaro's choice, ended the internal conflicts of the institute.
With the Anglo-Egyptian victory over the Mahdists, the Comboni Missionaries could resume their mission to Sudan. The congregation received the Papal Decree of Praise on 7 June 1895. ​Since the congregation was now mature and self-sufficient, Antonio Maria Roveggio, successor to Sogaro, in 1899 took on the responsibility of formation of new missionaries from the Jesuits. On 19 February 1910, the Holy See finally approved the institute and its constitutions.
The founder, beatified in 1996, was proclaimed a saint by Pope John Paul II on 5 October 2003.
Activity and expansion 
The Comboni Missionaries dedicate themselves to the missionary apostolate to the populations that are not yet or not sufficiently evangelized, especially in Africa. They are present in Europe (Austria, France, Germany, Ireland, Italy, Poland, Portugal, United Kingdom, Spain), Africa (Benin, Central African Republic, Chad, Democratic Republic of Congo, Ghana, Egypt, Eritrea, Ethiopia, Malawi, Mozambique, South Africa, South Sudan,Sudan, Togo, Uganda, Zambia), in the Americas (Brazil, Canada, Chile, Costa Rica, Ecuador, El Salvador, Guatemala, Mexico, Nicaragua, Peru), and Asia (Philippines, Macao, Taiwan).
The Mother House is in Via Luigi Lilio in Rome. At the end of 2008, the congregation had 328 houses with 1,803 religious, 1,296 of whom were priests.