The giant reed, Arundo donax is one of the worst invasive alien species globally, including South Africa, where it invades riparian areas across the country. Biological control is being considered to address the invasive potential and negative impacts of the weed. This study investigated the phylogeography of A. donax to guide the biological control program. To determine plant haplotype and genetic diversity, three regions of the chloroplast were sequenced and three microsatellite markers were analyzed in 40 samples from across the plant’s distribution in South Africa. It was determined that all populations of A. donax in South Africa were haplotype M1, which is the most widely distributed haplotype worldwide, believed to originate from the Indus Valley, Asia. In addition, no genetic diversity was found, indicating that all the A. donax populations in South Africa are essentially one clone. The results indicate that suitable biological control agents are likely to be found in the ancient native range of haplotype M1. This research has contributed to the global understanding of the phylogeography of A. donax and will guide the biological control program in South Africa.