A life-cycle greenhouse gas (GHG) emissions assessment is conducted on a novel, stable dimethyl ether (DME)-glycerol blend with propylene glycol (PG) cosolvent (i.e., Michigan DME blend II) with its DME content ranging between 40-50 wt %. The ratio of PG to glycerol is fixed at the minimum cosolvent to glycerol mass ratio (MCR) at each DME wt %. The system boundary of the assessment contained 7 different processes: (i) crude glycerol production; (ii) glycerol purification; (iii) PG production; (iv) DME production; (v) Michigan DME blending; (vi) Michigan DME blend transportation; and (vii) pump-to-wheels combustion. Twelve different pathways are established (i.e., 3 different cases for glycerol purification process and 4 different cases for DME production process) for the production of unit mass (1 kg) or unit energy (1MJ) of Michigan DME blend II, and the results are compared with each other. The pathway using high-purity crude glycerol product for glycerol purification (Case C) and DME production from animal manure (Case 4) showed the lowest well-to-wheels (WTW) GHG emissions (i.e., 45.8 gCO(2)e/MJ), which achieved about 50% GHG reduction from the petroleum-based diesel baseline. The pump-to-wheels combustion process was the biggest GHG emitting process (i.e., 34% of the WTW GHGs) for fossil-based DME cases while the crude glycerol production process was the biggest GHG emitting process (i.e., 44-55% of the WTW GHGs) for renewable DME cases. Propylene glycol production (i.e., 32% of WTW GHGs for renewable DME cases) and glycerol purification (i.e., 4-15% of WTW GHGs) also accounted for a significant portion. Adoption of regenerative farming methods, use of less carbon intensive hydrogen for PG production, and more efficient material and thermal energy utilization are suggested as the potential solutions to further reduce GHG emissions from the current LCA result of the Michigan DME blend II.