A novel type of effective microfine cement-based grout (EMCG) is designed for the complicated water-rich sand stratum. Superplasticizer (SP), compound excitation modulator (CEM), enhanced stabilizer (ES) and active activator (AA) were selected as optimizers. Through laboratory tests, main properties of EMCG i.e. fluidity performance, viscosity, bleeding rate, setting time, strength and volume stability were studied. Based on XRD mineral and SEM microstructure tests, hydration mechanism and microstructure of EMCG were studied. The results showed that the optimal parameters were 40% microfine fly ash (MFA), 14–18% microfine steel slag (MSS), 20–25% microfine slag (MS), 2–2.5% naphthalene-based SP (N), and 1–1.5% AA, 0.4–2.0% CEM and 6% ES. The 28d compressive strength of EMCG can reach 12.9–32.8 MPa. The 7 d strength can exceed 70% of 28 d strength. Through grouting injectability and reinforcement simulation tests, injectability of EMCG was acquired under different main influence factors i.e. sand particle size distribution, sand compactness, grout type, water-solid ratio (W/S), grouting pressure, etc. Quantitative relationships among enhancement strength or permeability coefficient and main influence factors were established. The microscopic slurry-rock interface reinforcement mechanism was obtained. Finally, based on field tests, the sealing and reinforcement effects of EMCG on water-rich sand stratum were acquired and discussed. Due to high overall performance and excellent engineering applicability of EMCG, it is an efficient and excellent cementitious grout especially for seepage prevention and reinforcement of water-rich sand stratum in geotechnical and underground engineering.