The Mackenzie Presbyterian Institute began its activities in 1870, when the couple of Presbyterian missionaries George and Mary Ann Annesley Chamberlain arrived in the city of São Paulo.

Mrs. Chamberlain received boys and girls for the school that was in its formation, asserting the principle that remains to this day: not to make any distinction as to sex, creed, or ethnicity. The following year, the American School was established, embryo of the School, that housed children of slaves and of traditional families.

In 1876, now on the corner of Ipiranga and São João streets, the American School implemented two new courses: Teaching-training School and the Philosophy Course. In 1879, Dona Maria Antonia da Silva Ramos, Baroness of Antonina, sold to the Reverend Chamberlain area of ​​her small ranch in Higienópolis. It was the beginning of a new phase.

The fame of the American School was not restricted to Brazil, reaching the ears of the American lawyer John Theron Mackenzie who, without ever coming to Brazil, left in testament a donation to the American Presbyterian Church to build an engineering school in Brazil. Thus, the name used until today was born: Mackenzie.

In February of 1896, the course of the School of Engineering Mackenzie began, with diplomas still issued by the University of New York. In the 1940s, new courses were created, such as the Faculty of Philosophy, Sciences and Arts (1946); Faculty of Architecture (1947); and the Faculty of Economic Sciences (1950). With these four higher education schools, in 1952, the Mackenzie is recognized as a university by the then president Getúlio Vargas. In 1955, the first class of the Faculty of Law began. 

In 1965, the Mackenzie named Esther de Figueiredo Ferraz as a rector, the first woman to take up this position in Brazilian universities. 

In 1970, the Faculty of Technology was created, supplying the demand for qualified professionals in superior courses of the area. 

Aiming at the overall formation of its students, Mackenzie offers the opportunity to remain in the institution from basic education to graduate studies, at the levels of specialization (lato sensu), master's and doctorate (stricto sensu), in the units of São Paulo, Alphaville/ Tamboré, Brasília, Campinas, Palmas, Rio de Janeiro, Castro, Dourados and Curitiba.