The formability at room temperature and low speed limits the application of aluminum alloy, while high strain rates positively improve the formability of materials. The constitutive behaviors of materials under high strain rates or impact loadings are significantly different from those under quasi-static conditions, while few constitutive models consider the effect of the mobile dislocation and forest dislocation evolution on the dynamic strain aging (DSA) over a wide strain-rate range. The 5052 aluminum alloy, of which the primary source of strain-hardening is dislocation–dislocation interaction, is widely used in manufacturing automotive covering parts and is considered one of the most promising alloys. Therefore, this study conducts uniaxial tensile tests on AA5052-O under conditions of temperatures ranging from 293 K to 473 K and strain rates ranging from 0.001 s−1 to 3000 s−1, and compares the stress–strain relationships of AA5052-O under different conditions to illustrate the constitutive relationship affected by the dislocation evolution over a wide strain-rate range. The Arrhenius model based on the thermal activation mechanism is modified and extended by considering the effects of dynamic strain aging (DSA), drag stress, and the evolution of mobile dislocation and forest dislocation. Thus, a new physics-based constitutive model for AA5052-O is proposed, which can well reflect the change in strain-rate sensitivity with the strain rate increasing. The mobile dislocation density and total dislocation density are predicted with a modified Kubin–Estrin (KE) model, and the influences of variable mobile dislocation on DSA and dislocation drag are discussed as well. In order to verify the reliability of the new constitutive model, the dislocation densities of the specimens before and after deformation are obtained with TEM and XRD, which are in good agreement with the predicted values. This study also compares the newly proposed model with classic constitutive models using multiple statistical evaluation methods, which shows that the new physics-based constitutive model has not only more clear physical meanings for its parameters but also has a higher prediction accuracy.