This paper presents a methodology for use of mechanistic–empirical design procedures to determine load equivalencies for various axle configurations and loads with a focus on oversize and overweight vehicles. The study uses the DARWin-ME system for pavement analysis and computation of equivalent damage factors (EDFs). In the context of the study, the EDFs for a given axle load and configuration consist of two partial factors: the axle load factor and the group equivalency factor. The framework adopted in this study defines a given axle load and configuration equivalent to a reference axle load based on equivalent pavement responses that results in the same distress level. The EDFs for single, tandem, tridem, and quad axles were evaluated for a wide spectrum of varying loads, and three failure criteria were applied: rutting, fatigue cracking, and roughness. Except in the case of rutting, there was no evidence that EDFs are affected by the structural capacity of the pavement sections. For single axles, it was found that thicker pavement structures are less sensitive to traffic loads. For tandem, tridem, and quad axles, the relationship was nonmonotonic. For fatigue cracking, a linear relationship between the axle load factor and the number of axles per axle group was observed. Finally, for roughness, the EDFs showed no systematic trend for the different structural numbers.