Droplets on inclined substrates can depin and slide freely above a critical substrate inclination angle. Pinning can be caused by topographical defects on the substrate, and understanding the influence of defect geometry on the pinning–depinning transition is important for diverse applications such as fog harvesting, droplet-based microfluidic devices, self-cleaning surfaces, and inkjet printing. Here, we develop a lubrication-theory-based model to investigate the motion of droplets on inclined substrates with a single three-dimensional Gaussian-shaped defect that can be in the form of a bump or a dent. A precursor-film/disjoining-pressure approach is used to capture contact-line motion, and a nonlinear evolution equation is derived which describes droplet thickness as a function of the position along the substrate and time. The evolution equation is solved numerically using an alternating direction implicit finite-difference scheme to study how the defect geometry influences the critical inclination angle and the shape of a pinned droplet. It is found that the critical substrate inclination angle increases as the defect becomes taller/deeper or wider along the direction lateral to the droplet-sliding direction. However, the critical inclination angle decreases as the defect becomes wider along the sliding direction. Below the critical inclination angle, the advancing contact line of the droplet at the droplet centerline is pinned to the defect at the point having maximum negative slope. Simple scaling relations that reflect the influence of defect geometry on the droplet retention force arising from surface tension are able to account for many of the trends observed in the numerical simulations.