A facile approach to synthesize poly(benzoxazole-co-imide)s without thermal rearrangement at high temperature is proposed. Poly(benzoxazole-co-imide)s with improved mechanical and solution-processable properties were prepared through polycondensation of 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) with three synthesized novel benzoxazole-containing diamines and a commercial diamine. These poly(benzoxazole-co-imide)s had high tensile strengths of 110.3–122.0 MPa and good elongation at break of 11.9–26.3%, good thermal stability and high glass transition temperatures (Tgs) of up 306 °C. The effect of chain isomerism on molecular packing and physical and gas transport properties of the poly(benzoxazole-co-imide)s was investigated. The para-connecting isomers exhibited higher molecular weights (Mws), better mechanical properties, higher Tgs, higher chain packing order and better overall performance for CO2/CH4 and CO2/N2 separations as compared to the corresponding meta-connecting ones. This study guides molecular architecture to improve particular membrane separation performance by introducing either para- or meta-connections into polymeric main chains.