The invention provides a large-dose multi-slug water plugging method. The method includes the steps that S1, active water is prepared, wherein a composite cleanup additive and a clay stabilizer are dissolved in clear water together, and dissolving is repeated several times so that the composite cleanup additive and the clay stabilizer are sufficiently dissolved, and the mass concentration of the composite cleanup additive and the clay stabilizer reaches 0.5%; S2, polymer microspheres are prepared, wherein the polymer microspheres are dissolved in clear water according to the mass concentrationof 1-5%, and dissolving is repeated several times so that the polymer microspheres are sufficiently dissolved; S3, gel is prepared, wherein the gel is dissolved in clear water according to the mass concentration of 1-5%, and dissolving is repeated several times so that the gel is sufficiently dissolved; and S4, cross-linked polymer gel is prepared, wherein polyacrylamide is dissolved in clear water according to the mass concentration of 0.2-0.4% and swells for at least 12 hours, a chromium cross-linking agent is added before water plugging construction according to the mass ratio of 1:1, andthe step is repeated several times. The method is high in operability, can effectively plug a water channel of a fractured intermediate-high-water-cut oil well, and successfully solves the problem that longitudinal remaining oil is used for plugging a breakthrough interval of the intermediate-high-water-cut oil well.