Developing green and effective solvents is of significant importance for the utilization of lignin. Here, we demonstrated that biomass-derived polar aprotic solvents can serve as co-solvents with poly-deep eutectic solvents (PDESs) for massively dissolving various lignin samples at room temperature. The pristine PDESs were composed of polyethylene glycol derivatives and levulinic acid, while all of them exhibited poor solubility to enzymatic hydrolysis lignin (EHL), sodium lignosulfonate (LS), and organosolv lignin (OL). With the further introduction of polar aprotic solvents, including dimethylisosorbide (DMI), dihydrolevoglucosenone (Cyrene), N-formylmorpholine (NFM), and propylene carbonate (PC), synergy between the polar aprotic solvents and PDESs dramatically increased lignin solubility to 96.82%. PC and DMI were more suitable for assisting the solubilization of EHL and OL, while Cyrene and PC were targeted at the solubilization of LS in PDESs, respectively. Moreover, a new unified co-solvent solubilization mechanism relative to the Kamlet–Taft empirical parameters was proposed. The novel polar aprotic/PDES systems provide a new avenue for boosting the high utilization of lignin.