Mamili was officially proclaimed on 1 March 1990, just a few days before Namibia gained independence. The name of the park refers to the seven chiefs of that name who have ruled over the Mafwe people living in this eastern part of the Caprivi region since 1864. Some also call the area Nkasa Lupala Park, in reference to the two dominant islands in the park.

This is the largest wetland with protected status in Namibia and is a haven for wetland species. When the floodwaters of the Kwando River are high, Mamili becomes like a mini-Okavango Delta. There are almost 1 000 buffaloes in Mamili, the largest concentration in the country. It is also an important corridor for elephants migrating from Botswana to Angola and Zambia, and is considered a core breeding area for wildlife that can disperse into neighbouring protected areas.