"There are millions of children, mostly young girls, who are victims of this hidden form of exploitation that often involves sexual abuse, mistreatment, and discrimination. It is real slavery," the pontiff said.
Addressing a crowd of 60,000 people in St. Peter's Square, Pope Francis urged "ever more effective measures to fight this true scourge".
He called it "a deplorable phenomenon constantly on the rise".
There are an estimated 10.5 million children worldwide working as domestic workers, according to figures published by the International Labour Organisation (ILO).
Six and a half million of these child labourers are aged between 5 and 14 years, and over 71 percent are girls, the ILO further added.