Sukkur is located on the west bank of the River Indus and has been an important strategic centre and trading route from time immemorial. Alor (or Aror, Sukkur) held the status of capital under the region of Musikanos, when Alexander invaded the region in 326 BCE. The ruins of this ancient town still exist, 8 km east of Rohri, in Sukkur district. The Rai Dynasty built a huge temple of Shiva. In 711 CE, the Arabs invaded Sindh, led by 17 year old Muhammad Bin Qasim, and Sukkur (including all of Sindh and lower Punjab) became part of the Umayyad Caliphate. 

Later Mughals and many semi-autonomous tribes ruled over Sukkur. The city was ceded to Mirs of Khairpur between 1809 and 1824. In 1833, Shah Shuja (a warlord of Kandahar, Afghanistan) defeated the Talpurs near Sukkur and later made a solemn treaty with the Talpur ruler, by which he relinquished all claims on Sindh. In 1843, the British (General Charles James Napier) defeated the Talpurs at the battles of Miani and Dubbo near Hyderabad. Sukkur, along with the rest of Sindh, was under British rule until the independence of Pakistan in 1947. The (current) district of Sukkur was constituted in 1901 out of part of Shikarpur District, the remainder of which was formed into the Larkana District. Sukkur saw a significant socio-economic uplift after the 1930s, when the British built the world’s largest barrage here on the Indus River, The district of Sukkur (whose name is derived from its headquarter Sukkur city) covers an area of 5,165 square kilometres. Geographically it is spanned from 27°05′ to -28°02′ north latitudes and from 68°47′ to 69°43′ east longitudes. The city of Sukkur is located at an altitude of 220 feet (67 m) from sea level, having terrestrial coordinates 68°52′ east and 27°42′ north. It is also the narrowest point of the lower Indus course.

Sukkur district shares its northern border with Shikarpur and the recently constituted Kashmore districts. Ghotki is located on the north-eastern side while Khairpur on the south. The border with India lies further east. Sukkur is also connected by road and by air with all major cities of Pakistan.