In this work, 2195 Al–Li alloys with various precipitation microstructures were obtained by homogenization treatment followed by air-cooling (AC), discontinuous cooling (DC), and furnace-cooling (FC), and then tested by hot compression at different temperatures. The results show that the flow stresses of all specimens decrease with temperature and the peak stresses of AC, DC and FC specimens decrease in order at the same temperature. For FC samples, coarse pre-precipitates diminish the deformation resistance due to the reduction of solid solution strengthening and precipitation strengthening. Dynamic softening at low temperatures is significantly greater than that at high temperatures, except for the anomalous softening of the FC specimen at 520 °C due to stress release by cracks. At 370–420 °C, the dynamic softening of the AC specimen is more significant than the other samples, resulting from dynamic precipitation and precipitate coarsening. Furthermore, there is considerable dynamic recrystallization (DRX) in FC samples and not in AC and DC samples, although their precipitates coarsen to similar levels at low temperatures. This suggests that DRX is associated with the particle-stimulated nucleation mechanism by regularly arranged precipitates. The banded or regularly arranged precipitates divide the Al matrix into multiple confined units, hindering dislocations and (sub)grain boundary movement, and thus promoting the development of sub-grains and DRX.