The charity, Unicef, estimates 147 million children have missed at least half of their in-person schooling.
Some vulnerable children, especially girls, have not returned to those schools that have reopened.
Unicef executive director Catherine Russell says children are “the hidden casualties of the pandemic”.
While children have been less vulnerable to the most serious health effects of coronavirus, their lives have been turned upside down by the school closures of the pandemic.
In March 2020, 150 countries around the world completely shut their schools, with partial closures in a further 10.
Two years later, 19 still have some of their schools closed.
In a further four – the Philippines, Honduras, Solomon Islands and Vanuatu in the South Pacific – at least 70% remain shut, the proportion Unicef categorises as full closure.
“We’re seeing children go back who were reading before, who now can’t read, who were doing numbers before, who now can’t do that,” Ms Russell told BBC News.
She fears most for those who have dropped out of school and risk becoming vulnerable to exploitation.
“Some children, because their families were so impoverished, were moved into the workforce,” she said.
“Girls also get moved into early marriage – and that’s a terrible fate.”
In the Philippines, where children have also faced restrictions on playing outside, a few schools started to reopen during the autumn but most pupils remain at home.
Chloe Almojuela Dikit, 13, has tried to keep up with her lessons online.
“I miss the teaching and the classmates and also the activities and schoolwork – just the things that we do in school,” she said.