City-level policies are increasingly recognized as key components of strategies to reduce transport greenhouse gas emissions. However, at a global scale, their total efficiencies, costs, and practical feasibility remain unclear. Here, we use a spatially-explicit urban economic model, systematically calibrated on 120 cities worldwide, to analyze the impact of four representative policies aiming at mitigating transportation GHG emissions, also accounting for their economic welfare impacts and health co-benefits. Applying these policies in all cities, we find that total transportation GHG emissions can be reduced by 28% in 15 years, compared with the baseline scenario. However, the consequences of the same policies vary widely between cities, with specific effects depending on the policy considered, income level, population growth rate, spatial organization, and existing public transport supply. Impacts on transport emissions span from high to almost zero, and consequences in terms of welfare can either be positive or negative. Applying only welfare-increasing policies captures most of the emission reductions: overall, they reduce emissions by 20% in 15 years. Our results highlight that there is no one-size-fits-all optimal policy to mitigate urban transport emissions but that cities can match their specific situation with a selection of mitigation policies: hence, we call for global climate mitigation models to better represent heterogeneity across cities.