Aims: To evaluate the effects of rice establishment, tillage and rice straw management on changes in soil enzyme activities and chemical properties in soil after three cycles of continuous rice-wheat system. Study Design: The experiment was laid in split plot design with three replications. Place and Duration of Study: PAU, Ludhiana, 2010-2013. Methodology: The experiment was started during kharif season of 2010. The design of an experiment was having 12 treatments with 3 replications. The main plot treatments in rice (zero till direct seeded rice, ZT-DSR; conventional till direct seeded rice, CT-DSR; zero till direct transplanted rice, ZT-DTR and puddled transplanted rice, PTR) and three sub-plot treatments in wheat (conventional till wheat without rice straw, CTW-R; ZT wheat without rice straw, ZTW-R, and ZT wheat with rice straw retained as surface mulch using Happy Seeder, ZTW+R). Results: Zero tillage with rice straw retention (ZTW) as surface mulch (+R) increased wheat yield by 9% and 15% compared with conventional tillage (CTW) and ZTW with no residue (-R). Significantly higher dehydrogenase, fluorescein diacetate, alkaline phosphatase, phytase and urease activities were recorded under ZTW+R compared with ZTW/CTW-R in 0-5 cm soil layer. Organic carbon, Olsen-P, available K and DTPA-extractable micronutrients (Zn, Fe, Mn and Cu) in the surface 0-5 cm soil layer were significantly higher in ZTW+R compared with ZTW/CTW-R. Soil enzyme activities were significantly and positively correlated with each other, soil organic carbon, Olsen-P and grain yield of wheat. Conclusion: We concluded that RCTs (ZTW and rice residue retention) improve soil enzyme activities and chemical properties in surface 0-5 cm soil layer and enhance productivity and sustainability of rice-wheat system.