The dynamic mechanical behavior, fracture characteristics, and microstructural evolution of high-strength weldable aluminum-scandium (Al–Sc) alloy were investigated using a compressive split Hopkinson pressure bar at strain rates of 1.3 × 103, 3.6 × 103, and 5.9 × 103 s−1, respectively, and temperatures of −100, 25, and 300 °C. The results showed that the flow stress, work hardening rate, and strain rate sensitivity increase with increasing strain rate but decrease with increasing temperature. Conversely, the activation volume and activation energy increase as the temperature increases or the strain rate decreases. Moreover, the fracture strain decreases with increasing strain rate and decreasing temperature. It was shown that the Zerilli–Armstrong face-centered-cubic (fcc) constitutive equation provides accurate predictions of the mechanical response of the Al–Sc alloy under the considered strain rate and temperature conditions. Scanning electron microscopy observations revealed that the fracture surfaces of the impacted specimens are characterized by transgranular dimpled features, which are indicative of a ductile failure mode. Moreover, transmission electron microscopy observations indicated the presence of both fine and coarse randomly dispersed precipitates within the matrix and at the grain boundaries. It was found that an increasing strain rate reduces the size of the dislocation cells within the impacted Al–Sc microstructure and therefore increases the dislocation density. However, at higher temperatures, the dislocations are annihilated, leading to a reduction in the dislocation density and a corresponding increase in the dislocation cell size. The variations observed in the size and density of the dislocation cells were found to be consistent with the dynamic tendencies noted in the stress–strain response of the Al–Sc alloy.