In front of a congregation of 30, 000 worshippers who gathered at Saint Peter's Square, the pontiff praised their "philosophy of charity and service."
Thousands were hearing-impaired worshippers who came to pay homage to Filippo Smaldone (1848-1923), an Italian priest who founded institutes for the deaf.
A large Mexican contingent also came to witness the canonisation of Rafael Guizar Valencia, dubbed by Benedict XVI the "Bishop of the Poor".
The prelate worked during the Mexican revolution of 1910 and through the years of open conflict between the Catholic Church and political authorities.
Rafael Guizar Valencia was the great-uncle of Marcial Maciel, founder of the Legions of Christ movement, who was recently forced by the Vatican to withdraw from public life after repeated allegations of sexual abuse.
French and US worshippers paid hommage to Anne-Therese Guerin, otherwise known as Mother Theodore Guerin, who was born in 1798 in France and moved to Illinois in 1840 where she founded the congregation of the Sisters of Providence of Saint-Mary-of-the-Woods.
Italian nun Rosa Venerini was the fourth to be canonised.
In 1685 she opened the first public girls' school in her country.
Benedict XVI said he wished that young people would take the "exemplary testament" of the four religious men and women and "adopt their philosophy of charity and service, the only way to save the world".
Contrary to his usual style, the Pope did not digress at any point from the written text of his homily, or from the preceding Angelus message which he also dedicated to the four saints.