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Changes in the natural landscape and the indiscriminate use of pesticides can have a major impact on aquatic environments and have contributed to the worldwide decline of amphibian populations. In the present study, we sampled tadpoles of three anuran amphibians (Boana albopunctata, Physalaemus cuvieri, and Dendropsophus minutus) from ponds in six different agricultural landscapes of the Brazilian Cerrado savanna and evaluated whether and to what extent genotoxic and mutagenic damage was related to land use (the amount of forest and agricultural remnants, and related physicochemical factors) and the presence of pesticides in the water of the study ponds. We also evaluated the hepatotoxicity in P. cuvieri, which was the most abundant species at five of the six sampling points. Clomazone and atrazine were the most common pesticides found in the ponds. The B. albopunctata and P. cuvieri tadpoles presented similar patterns of DNA damage among the sampling points. The least DNA damage was found in the D. minutus tadpoles, although this species was present in only one of the study ponds. More binucleated and anucleated cells were observed in B. albopunctata, but there was no significant variation among species in terms of the number of micronuclei or other erythrocytic nuclear abnormalities. Land use and physicochemical factors did not explain the variation in the DNA damage observed in the three anurans. The hepatotoxicity analyses of P. cuvieri revealed the presence of a series of alterations, including the enlargement of the sinusoids, vacuolization of the hepatocytes, the infiltration of inflammatory cells, hepatic steatosis, and dilation of the blood vessels. The interaction between physicochemical factors and the biomarkers analyzed in the present study is complex. In particular, it will be important to better elucidate which factors are contributing, either directly or indirectly, to the decline of anuran amphibian populations, especially in threatened biomes, such as the Brazilian Cerrado. In this case, we would encourage further in situ studies that assess the ecotoxicology of the landscape, together with the systematic monitoring of aquatic environments, to guarantee the long‐term integrity of amphibian populations, and those of other organisms that play an essential functional role in the ecosystem. Environ Toxicol Chem 2023;42:2422–2439. © 2023 SETAC [ABSTRACT FROM AUTHOR]