Major distresses such as rutting, fatigue, and thermal cracking are facing asphalt pavement structures due to continuous heavy traffic loading and climate change. The modification of asphalt binders (one of the main components of the asphalt paving mix) has the potential to mitigate distresses through using different additives. Polymer modified asphalt (PMA) binders showed a noticeable resistance to pavement distresses as reported in previous studies. The present study aims to evaluate the effect of polymer modification on the rheological properties of asphalt binders through laboratory tests. The polymers included styrene-butadiene-styrene (SBS) and epolene emulsifiable (EE2) types. The 60/70 binder was used as a control for comparison. The Mechanistic-Empirical Pavement Design Guide (MEPDG) was also utilized to simulate the effect of PMA binders on the rheological properties under different climatic conditions and structural capacities. Additionally, the MEPDG was further utilized to compare the effect of asphalt binders on rheological properties using four different binder input levels. Findings of the study showed that laboratory tests experienced varying outcomes regarding the most efficient asphalt binder by means of distresses resistance. However, the MEPDG evaluation showed that the overall ranking of asphalt binders positively impacting the rheological properties was as following: (1) 4.5% EE2 PMA, (2) 4% EE2 PMA, (3) 60/70 binder, (4) 5% SBS PMA, and (5) 4% SBS PMA binders. Furthermore, statistical analysis illustrated that the effect of using different binder input levels on the performance of pavement varied relatively to the evaluated distresses. The analysis showed that using different binder input levels would affect, to a certain extent, the asphalt binder influence on rheological properties only when evaluating rutting and fatigue distresses. Therefore, it is recommended that precise asphalt binder inputs, that is, shear complex modulus (G*) and phase angle (δ) are used when designing pavement structures in regions with hot and mild climate conditions.