Pereskia aculeata Miller (Cactaceae) is a primitive leafy cactus indigenous to Central and South America that has become a problematic invasive alien plant elsewhere in the world. In South Africa the plant invades established forests, clearings, thickets and plantations along the southern and eastern higher rainfall regions of the country. Pereskia aculeata is a woody vine (liana) that scrambles up existing vegetation competing for resources, often causing canopies to collapse under its weight. Similarly, to other invasive vines, mechanical and chemical control is challenging due to the plant growing intertwined with indigenous vegetation and therefore, biological control using specialist insect herbivores is considered essential for its management. Increasing atmospheric carbon dioxide (CO2) concentrations are expected to favour weeds, however this response is likely to be influenced by projected changes to rainfall patterns. Pereskia aculeata were grown from truncheons for five months at three CO2 concentrations: 250 (sub-ambient), 400 (ambient) and 600 (elevated) ppm under two watering regimes, reduced water (200 ml wk(-1)) and ambient-water (400 ml wk(-1)), to simulate two annual rainfall scenarios of similar to 520 mm (below present optimal) and similar to 1040 mm (present optimal), respectively. Elevated CO2 (eCO(2)) increased growth rates, biomass accumulation and reduced leaf nutritional quality (nitrogen content and C:N ratios), but only for ambient-water treatment plants. Nevertheless, higher photosynthetic rates under eCO(2) improved water use efficiency for both water treatments, which was greatest for the reduced-water treatment plants. Management of P. aculeata in South Africa is already extremely challenging and with rising atmospheric CO2, P. aculeata has the potential to become more problematic, particularly in optimal rainfall areas. Furthermore, with improvements in water use efficiency, P. aculeata has the potential to expand into lower rainfall areas, although it is unlikely to pose the same risk as those plants invading higher rainfall sites.