It was built by order of Hafsa Hatun, the daughter of Isa Bey Evrenosoğlu, but named after Hamza Bey, the Beylerbey of Rumeli. It was damaged in later earthquakes and fires and was rebuilt in 1620. Following the population exchange between Greece and Turkey, the mosque no longer functioned as a religious building and became the property of the National Bank of Greece. It initially housed various military services, and although it was declared a protected monument in 1926, it was sold in 1928 to private owners. The building was subsequently used for several decades as a shopping centre and cinema, and suffered extensive modifications. The mosque was handed over to the Greek Ministry of Culture in 2006, and restoration work has been under way since.