We report on the use of molecular acceptors (MAs) and donor polymers processed with a biomass-derived solvent (2-methyltetrahydrofuran, 2-MeTHF) to facilitate bulk heterojunction (BHJ) organic photovoltaics (OPVs) with power conversion efficiency (PCE) approaching 15%. Our approach makes use of two newly designed donor polymers with an opened ring unit in their structures along with three molecular acceptors (MAs) where the backbone and sidechain were engineered to enhance the processability of BHJ OPVs using 2-MeTHF, as evaluated by an analysis of donor-acceptor (D-A) miscibility and interaction parameters. To understand the differences in the PCE values that ranged from 9-15% as a function of composition, the surface, bulk, and interfacial BHJ morphologies were characterized at different length scales using atomic force microscopy, grazing-incidence wide-angle X-ray scattering, resonant soft X-ray scattering, X-ray photoelectron spectroscopy, and 2D solid-state nuclear magnetic resonance spectroscopy. Our results indicate that the favorable D-A intermixing that occurs in the best performing BHJ film with an average domain size of ∼25 nm, high domain purity, uniform distribution and enhanced local packing interactions - facilitates charge generation and extraction while limiting the trap-assisted recombination process in the device, leading to high effective mobility and good performance.