Pope Francis and the Catholic Church has traditionally opposed divorce, but said there was even greater reason for a split to be accepted if a partner was being abused.
The remarks were made ahead of the bishops' conference that will take place in the autumn.
"There are cases in which separation is inevitable," he said during his general audience.
The pontiff said: "Sometimes, it can even be morally necessary, when it's about shielding the weaker spouse or young children from more serious injuries caused by intimidation and violence, humiliation and exploitation, neglect and indifference."
The Church stressed it needed to learn how to best help these families to avoid children becoming "hostages of daddy or mummy."
Earlier in the week the Vatican released its working paper on the family.
The document stated that the route for divorced people to be given Communion, something currently prohibited by the Church, "requires further discussion".
It suggested that couples could commit to remain chaste in marriage as a condition of receiving the sacrament.
Bishops previously met to discuss similar issues last year but agreement could not be reached on key issues.