Study providing the most comprehensive assessment of amphibian and reptile response to land-use change in Madagascar. Abstract: Large expanses of tropical rainforest have been converted into agricultural landscapes cultivated by smallholder farmers. This is also the case in north‐eastern Madagascar; a region that retains significant proportions of forest cover despite slash‐and‐burn shifting hill rice cultivation and vanilla agroforestry expansion. The region is also a global hotspot for herpetofauna diversity, but how amphibians and reptiles are affected by land‐use change remains largely unknown. Using a space‐for‐time study design, we compared species diversity and community composition across seven prevalent land uses: unburned (old‐growth forest, forest fragment, and forest‐derived vanilla agroforest) and burned (fallow‐derived vanilla agroforest, woody fallow, and herbaceous fallow) land‐use types, and rice paddy. We conducted six comprehensive, time‐standardized searches across at least 10 replicates per land‐use type and applied genetic barcoding to confirm species identification. We documented an exceptional diversity of herpetofauna (119 species; 91% endemic). Observed plot‐level amphibian species richness was significantly higher in old‐growth forest than in all other land‐use types. Plot‐level reptile species richness was significantly higher in unburned land‐use types compared with burned land‐use types. For both amphibians and reptiles, the less‐disturbed land‐use types showed more uneven communities and the species composition in old‐growth forest differed significantly from all other land‐use types. Amphibians had higher forest dependency (38% of species occurred exclusively in old‐growth forest) than reptiles (26%). Our analyses thus revealed that the two groups respond differently to land‐use change: we found less pronounced losses of reptile species richness especially in unburned agricultural habitats, suggesting that reptiles are less susceptible to land‐use change than amphibians, possibly due to their ability to cope with hotter and drier microclimates. In conclusion, our findings emphasize existing conservation opportunities – especially for reptiles – in extensive agricultural landscapes while highlighting the precarious situation of amphibians in disappearing old‐growth forests.