Karnali Province is one of the seven federal provinces of Nepal formed by the new constitution, which was adopted on 20 September 2015. The total area of the province is 27,984 square kilometres (10,805 sq mi), making it the largest province in Nepal with 18.97% of the country's area. According to the 2011 Nepal census, the population of the province was 1,570,418, making it the least populous province in Nepal. The province borders the Tibet Autonomous Region of China to the north, Gandaki Province to the east, Sudurpashchim Province to the west, and Lumbini Province to the south. Birendranagar with a population of 154,886 is both the province's capital and largest city.

The Karnali River, called Ghaghara River in India, Mapcha Tsangpo in Tibet, and the lower Ghaghara in Awadh called Sarayu River, is a perennial trans-boundary river that originates in the northern slopes of the Himalayas in the Tibetan Plateau, cuts through the Himalayas in Nepal and joins the Sharda River at Brahmaghat in India. Together they form the Ghaghara River, a major left-bank tributary of the Ganges. With a length of 507 km (315 mi), it is the longest river in Nepal. The total length of the Ghaghara up to its confluence with the Ganges at Revelganj in Bihar is 1,080 km (670 mi). It is the largest tributary of the Ganges by volume and the second largest by length after Yamuna.