Aiming to gain knowledge in the epoxy-bitumen modification mechanisms, this work explores the effects that epoxy concentration and ambient curing exert on the physico-chemistry and thermo-rheological properties of epoxy-modified binders. Process rheokinetics of epoxy-bitumen blends indicates that binder short-term modification (i.e., during processing) is accelerated by epoxy concentration. Furthermore, a synergistic effect of epoxy concentration and ambient curing is found during long-term modification (i.e., during curing at ambient conditions). As a result, viscous and viscoelastic rheological properties of binders are enhanced at medium/high in-service temperatures, at least, after one month of curing. FTIR (Fourier Transform Infrared spectroscopy) tests and SARAs (Saturates, Aromatics, Resins and Asphaltenes) analysis confirm the existence of esterification/etherification reactions between epoxy oxirane groups and the carbonyl groups available in aromatic and resin molecules. Thus, the new high molecular weight compounds increase the asphaltenic fraction of modified bitumen. Likewise, nonreversing heat flow curves obtained by modulated calorimetry corroborate the formation of such highly structured domains responsible for the final binder performance.