In this work, acrylonitrile and methyl acrylate copolymer [P(AN−MA)] was prepared by mixed solvent precipitation in a millimeter-scale microchannel reactor. In the range of 30 × 10 4 −60 × 10 4 g/mol, P(AN−MA) is characterized by a controllable molecular weight and a narrow polydispersity index (<1.3). It was found that the composition of P(AN−MA) was controlled by the ratio of dimethyl sulfoxide (DMSO)/H 2 O of the mixed solvent. This resulted from the different solubilities of AN in various DMSO/H 2 O ratios of the mixed solvent, leading to the change of AN/MA involved in the polymerization. The content of MA in the P(AN−MA) increased with a higher H 2 O content in the mixed solvent. The polymerization process of P(AN−MA) in the microchannel reactor follows a tertiary granulation mechanism, as shown by the morphology of P(AN−MA) precipitated particles. In addition, the increase of H 2 O content in the mixed solvent is favorable to improving particle morphology. However, it is difficult to control the flow state of the particles in the pipeline with a high H 2 O content. Therefore, 60 wt % H 2 O content is the optimum process condition. On this basis, the sedimentation of particles on the reactor wall was reduced, and pipe clogging was significantly improved by process optimization.