South Africa is a mega-diverse country situated at the southern tip of Africa flanked by two unique marine systems, one cool and one warm. Species introductions to the region have also been diverse. Given the major and growing threat to biodiversity and ecosystem functioning from biological invasions, there has been significant research on this topic. Biological invasions continue to expand and new species continue to arrive. Climate change is expected to affect invasions directly, influencing species’ distributions according to individual species’ tolerances and interactions with other species; and indirectly, through new introductions, and by altered pathways linked to human responses to climate change. The uncertainty relating to climate projections has narrowed considerably since the release of the Intergovernmental Panel on Climate Change Sixth Assessment Report, permitting a more focused assessment of its potential interaction with the impacts of biological invasions than was possible before. This chapter summarizes the projected changes for rainfall and temperature in the medium and long term using a middle-of-the-road socio-economic scenario based on ‘downscaled’ projections. Overall, projected shifts in climate, even over the long term, are less extreme than had previously been projected in national and regional assessments for South Africa, although the rate and extent of change is projected to be more extreme for southern African regions north of South Africa. Future biological invasions can be divided into: (i) expansion of existing invasions; (ii) new invasions that result from changes in the nature, volume and timing of trade and travel; and (iii) invasions that result from climate change mitigation and adaptation such as carbon sequestration projects and assisted migration. Expansion of native species, notably ‘bush encroachment’ in savannas, is also predicted to increase. We discuss likely patterns of change in terrestrial, freshwater and marine systems, considering first the change in current invasions and native species and then changes in pathways that are likely to affect future invasions in each realm. Species losses and gains are expected in all realms. On land, rising atmospheric CO2 has likely already facilitated widespread increases in cover of indigenous tree and shrub species, and may also exacerbate invasions of alien woody plants. Managing invasions in the future will require significant efforts in pathway control. Careful balance in permitting and even facilitating range expansions, while controlling undesirable native range expansions and preventing the introduction and expansion of generalist, highly invasive alien species is paramount. Policies aimed at using indigenous species in rehabilitation and carbon sequestration projects, as well as cross-border collaboration on biosecurity and biodiversity safeguards, are critical.