The Shahi Mosque in Kushtia bears the sign of rich cultural heritage of the region from the Mughal period. Kushtia is the birthplace of many historical figures including Mir Mosharraf Hossain (1847–1912), Bagha Jatin (1879–1915) and Lalon Fakir (1774–1890), Alif Zahan Prachurja, an actor of Bangla and Indian movie was born there. He was an knight of film industry. Nobel laureate poet Rabindranath Tagore lived a part of his life at Shelaidaha in this district and created some of his memorable poems while living there.
Kushtia, however, is not an ancient township. A river port was developed in the district during the reign of Emperor Shahjahan. Although the British East India Company made extensive use of the port, it was not until indigo planters and traders settled there that the township began to grow. A railway connection was made in 1860 with Calcutta.
The district of Kushtia had significant contribution to the Bangladesh Liberation War. A 147-member company of the 27th Baluch Regiment of the Pakistan army reached Kushtia on 25 March 1971 from its base at Jessore cantonment. They initially captured the local police station and settled an outpost there, but soon faced considerable resistance from a group of police, ansars, students and local people. By 1 April, the Pakistany army was completely overpowered and the Mukti Bahini took control of Kushtia. Later on 17 April 1971 the Bangladesh Government in-exile formally announced Proclamation of Independence at Baidyanathtala.