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Whole-genome duplication is a common macromutation with extensive impacts on gene expression, cellular function, and whole-organism phenotype. As a result, it has been proposed that polyploids have “general-purpose” genotypes that perform better than their diploid progenitors under stressful conditions. Here, we test this hypothesis in the context of stresses presented by anthropogenic pollutants. Specifically, we tested how multiple neotetraploid genetic lineages of the mostly asexually reproducing greater duckweed (Spirodela polyrhiza) perform across a favorable control environment and 5 urban pollutants (iron, salt, manganese, copper, and aluminum). By quantifying the population growth rate of asexually reproducing duckweed over multiple generations, we found that across most pollutants, but not all, polyploidy decreased the growth rate of actively growing propagules but increased that of dormant ones. Yet, when considering total propagule production, polyploidy increased tolerance to most pollutants, and polyploids maintained population-level fitness across pollutants better than diploids. Furthermore, broad-sense genetic correlations in growth rate among pollutants were all positive in neopolyploids but not so for diploids. Our results provide a rare test and support for the hypothesis that polyploids are more tolerant of stressful conditions and can maintain fitness better than diploids across heterogeneous stresses. These results may help predict that polyploids may be likely to persist in stressful environments, such as those caused by urbanization and other human activities.