The difference of enzymatic degradation behavior between Poly (butylene succinate-co-diethylene glycol succinate) (PBS-co-DEGS) and Poly (butylene succinate-co-butylene diglycolic acid) (PBS-co-BDGA) was studied in a Tetrahydrofuran (THF)/toluene mixed system by Novozym 435 (N435, immobilized Candida Antarctica lipase supported on acrylic resin) catalysis for 30 h. These two copolymers (modified with alcoholic acid by ether linkage) were synthesized by melt polycondensation and characterized by 1H NMR. The average molecular weight and thermal property before and after degradation were determined by gel permeation chromatography (GPC) and thermogravimetric analysis (TGA), respectively. Results revealed that end-chain degradation of DEG20 (20% content diethylene glycol of diols) and intramolecular random degradation of DGA20 (20% content diglycolic acid of diacids) both occurred at the same time from 0 h to 12 h. TGA curves show that after degradation by N435, the T-5% of both copolymers decreased from about 300 °C to below 210 °C. In degradation products (linear and cyclic oligomers, no monomer was appeared below 10 degree of polymerization. According to the molecular docking results, the free binding energy between PC lipase and substrate was in the order of BDGAB < DEGSDEG < BSDEG < BSB. Thus, the enzymatic degradability of PBS-co-DEGS is more effective than that of PBS-co-BDGA.