Belgium's bishops conference previously said the pope had been invited to attend celebrations for the 600th anniversary of the Catholic university of Louvain.
The university was founded in 1425, but is holding events throughout the 2024-2025 academic year.
"His Holiness Pope Francis will make an apostolic journey to Luxembourg on September 26 and in Belgium from September 26 to 29, going to Brussels, Louvain and Louvain-la-Neuve," the Vatican said in a statement.
The last papal visit to Belgium was in 1995, when John Paul II attended the beatification in Brussels of 19th century Flemish priest Jozef De Veuster, known as Father Damien.
The announcement of the visit comes just weeks after Pope Francis intervened in an sexual abuse scandal in Belgium's Catholic church.
In March, the bishops' conference revealed the pontiff had defrocked a disgraced Belgian bishop, Roger Vangheluwe, 87, who had 14 years ago admitted to years of child abuse.
Francis has made combating sexual assault in the church one of the main missions of his papacy, and insisted on a "zero tolerance" policy in the wake of multiple wide-reaching scandals.
The bishops' conference on Monday welcomed news of the pope's "exceptional" visit, saying it "greatly rejoices" at his looming arrival.
"All the more so because the Pope visits very few European countries, and even fewer in Western Europe," added Brussels archbishop and conference president Luc Terlinden.
Francis had previously indicated he would be visiting Belgium, but the timing may raise questions.
The trip will come less than a fortnight after the pontiff returns from an ambitious trip to Indonesia, Papua New Guinea, East Timor and Singapore between September 2 and 13.
Covering around 30,000 kilometres (18,600 miles) in total, the Asia trip is the longest for the Argentine pontiff since he became head of the Catholic Church in 2013.
It will also be the first abroad since Francis went to Marseille, France in September 2023, and could test his increasingly fragile health.
The pontiff, who uses a wheelchair, has suffered increasing health problems in recent years, from knee pain to surgery for a hernia and on his colon.
He visited the Italian city of Verona at the weekend, following a trip to Venice in April.
