Mountain roads in developing countries are known to increase landslide occurrence due to often inadequate drainage systems and mechanical destabilization of hillslopes by undercutting and overloading. This study empirically investigates landslide initiation frequency along two paved interurban highways in the tropical Andes of southern Ecuador across different climatic regimes. Generalized additive models (GAM) and generalized linear models (GLM) were used to analyze the relationship between mapped landslide initiation points and distance to highway while accounting for topographic, climatic and geological predictors as possible confounders. A spatial block bootstrap was used to obtain non-parametric confidence intervals for the odds ratio of landslide occurrence near the highways (25 m distance) compared to a 200 m distance. The estimated odds ratio was 18–21 with lower 95% confidence bounds > 13 in all analyses. Spatial bootstrap estimation using the GAM supports the higher odds ratio estimate of 21.2 (95% confidence interval: 15.5–25.3). The highway-related effects were observed to fade at about 150 m distance. Road effects appear to be enhanced in geological units characterized by Holocene gravels and Laramide andesite/basalt. Overall, landslide susceptibility was found to be more than one order of magnitude higher in close proximity to paved interurban highways in the Andes of southern Ecuador.