A study of foraminiferal assemblages was carried out in 24 sediment samples collected from the Montevideo coastal zone (south-eastern coastal region of South America) to assess the response of the benthic foraminifera to the polluted sediments. The area is affected by different pollutants such as sewage, hydrocarbons and heavy metals derived from different sources. Biological data were analyzed with multivariate techniques of cluster analysis and a principal component analysis (PCA) was performed for abiotic factors. The results allowed the recognition of different species assemblages corresponding to different sub-environments, which reflected the prevalent ecological conditions. The Montevideo Bay, particularly, its inner part showed an extremely poor foraminiferal fauna—including a totally azoic station—and high percentages of abnormal tests, when compared with the adjacent Punta Carretas and Punta Yeguas zones. Mean faunal density showed a strong relationship with organic matter, oxygen and heavy metal concentrations, as well as redox potential and pH values of each sub-environment. Although the adjacent zones presented a moderate pollution degree, it was noticed that a positive effect on the foraminiferal density specially on Ammonia tepida, caused by the sewage pipe located in Punta Carretas, a pure organic contamination. Differences among foraminiferal assemblages seemed to be related to the combined action of the several kinds of pollutants and the natural abiotic variables, like the rapid salinity changes that occurred in this area.