In the time of the first Roman Emperor Augustus the fortress was the most north-eastern point of Moesia on the frontier with the Thracian kingdom.

The available data determine its origin in 1086, when part of the Paulician population after the suppression of the Thracian uprising left the surroundings of Plovdiv and settled near the destroyed and depopulated ancient Roman fortress Dimum (Dum).

According to Lyubomir Miletich after the pogrom of the Chiprovtsi uprising in 1688, about 2,000 people from Belene moved to Wallachia to escape the Turkish atrocities.

Belene is the birthplace of Blessed Bishop Eugene Bosilkov (1900–1952), a martyr for the faith and beatified on 15 March 1998 in St. Peter's Basilica by Pope John Paul II In the Church of the Nativity of the Blessed Virgin Mary is the Sanctuary with a piece of the relics of Monsignor Bosilkov - a place of worship for believing Christians.

Belene was proclaimed a town in 1964,[3] which is celebrated every year in the first week of September with a market and cultural events.

In 2002, the Government decided to resume the Belene NPP Project and in 2005, the Council of Ministers issued a decision for construction of two 1000 MW units.

In 2018, the Minister of Energy was assigned to again explore possibilities for construction of the Belene NPP until it was interrupted in 1990 due to the severe economic crisis that followed the fall of communism in the country.

[4] There are plans to start construction again as a replacement for reactors 3 and 4 at Kozloduy Nuclear Power Plant, which Bulgaria shut down as a condition for EU membership.

Belene was the focal point for the feature documentary film The Mosquito Problem and Other Stories by Andrey Paounov.

[5] The film features some of the town's characters, highlighting their daily plight of a nuclear plant of empty promises and a year-round mosquito epidemic.