The town is positioned along the R61 (future N2 Wild Coast Toll Route) leading to Mthatha to the west and Port Shepstone to the north-east.

By 1894 European settlers started settling in Lusikisiki after Mpondoland was annexed by the Cape Colony and a magistrate took up residence there with a military camp established as well.

[3][4] In 1953 the South African Apartheid government made attempts to persuade the people of Lusikisiki to accept the rule of Bantu authorities which they had established.

The government worked with Paramount Chief King Botha Sigcau to attempt to start a rehabilitation scheme in Pondoland.

The area lies within Forest and Indian Coastal Thicket biomes, and White Milkwood (Sideroxylon inerme) are common.