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Invasive alien species are responsible for a high economic impact on many sectors worldwide. Nevertheless, there is a scarcity of studies assessing these impacts in Central and South America. Investigating costs of invasions is important to motivate and guide policy responses by increasing stakeholders’ awareness and identifying action priorities. Here, we used the InvaCost database to investigate (i) the geographical pattern of biological invasion costs across the region; (ii) the monetary expenditure across taxa and impacted sectors; and (iii) the taxa responsible for more than 50% of the costs (hyper-costly taxa) per impacted sector and type of costs. The total of reliable and observed costs reported for biological invasions in Central and South America was USD 102.5 billion between 1975 and 2020, but about 90% of the total costs were reported for only three countries (Brazil, Argentina and Colombia). Costs per species were associated with geographical regions (i.e., South America, Central America and Islands) and with the area of the countries in km2. Most of the expenses were associated with damage costs (97.8%), whereas multiple sectors (77.4%), agriculture (15%) and public and social welfare (4.2%) were the most impacted sectors. Aedes spp. was the hyper-costly taxon for the terrestrial environment (costs of USD 25 billion) and water hyacinth (Eichhornia crassipes) was the hyper-costly taxon for the aquatic environment (USD 179.9 million). Six taxa were classified as hyper-costly for at least one impacted sector and two taxa for at least one type of cost. In conclusion, invasive alien species caused billions of dollars of economic burden in Central and South America, mainly in large countries of South America. Costs caused by invasive alien species were unevenly distributed across countries, impacted sectors, types of costs and taxa (hyper-costly taxa). These results suggest that impacted sectors should drive efforts to manage the species that are draining financial sources.