The effects of the microstructure and the strain rate on the compression behavior of the Al0.1CoCrFeNiTi x (x = 0.1, 0.3, and 0.5 in molar ratio) high-entropy alloys (HEAs) are investigated. Compared with the Al0.1CoCrFeNiTi0.1 with the single-phase face-centered cubic (FCC) structure and the Al0.1CoCrFeNiTi0.3 HEAs, both the yield strength (YS) and the work hardening ability of the Al0.1CoCrFeNiTi0.5 HEA are enhanced significantly under the quasistatic condition. This is due to a combination of the solid-solution strengthening and sigma-phase precipitation hardening mechanisms. The strong work hardening of the Al0.1CoCrFeNiTi0.1 HEAs under quasistatic loading is attributed to the existence of the dislocation substructures (high-density dislocation walls and dislocation cells) and the deformation twinning accompanying homogeneous deformation. A significant strain rate sensitivity on the YS is obtained as a result of the phonon drag effect under dynamic loading. Different from the quasistatic condition, the dynamic grain refinement and the nanoscale twins inside the grains are the main microstructure characteristics in the dynamic deformation process.