Road networks are permanent manmade features altering the landscape structure and subsequently influence regional landscape ecology. Taking south-western foothills of Central Himalaya, as a case, this study assessed the spatio-temporal variations in landscape structure and landscape ecological risk (LER) influenced by the road network and topography. The relationship between LER and accessibility factors (distance to different road-types and road kernel density) and topographical factors (elevation and slope) were explored using ordinary least square (OLS) regression and geographically weighted regression (GWR) model. Our results indicate that high-risk LER zones are closer to the road network. This is also in conjunction with increasing built-up areas adjacent to the road network. Regression analysis using GWR model better explained the relationship between LER (dependent variable) and distance from different road-types (independent variables) as compared to OLS with a significant correlation at 1\% confidence interval. The spatial variations in the interrelation between dependent and independent variables were explained using quantified coefficients estimated by the GWR model. The estimation and visualization of spatial associations between landscape structure, LER, and road network provided in our study can act as a baseline for developing a guideline for sustainable infrastructure development and management of ecologically vulnerable landscapes across the tropical world. © 2020 Taylor & Francis Group, LLC.