Even though wind, water depth, and shear stress are important factors governing sediment resuspension in lakes, their actual relations to total suspended solids (TSS) distribution in natural environments have not been well elucidated. This study aims to elucidate the impact of the wind on the spatio-temporal variation of TSS in Tonle Sap Lake, Cambodia, during low-water (March and June, <1 m) and high-water (September and December, 8–10 m) seasons. To this end, wind and TSS data for December 2016 and March, June, and September 2017 were collected and analyzed. For spatial interpolation of wind speed, the inverse distance weighted method was found to be better (R2 = 0.49) than the vectorized average (R2 = 0.30) and inverse of the ratio of distance (R2 = 0.31). Spatial interpolation showed that the wind speed and direction on the lake were <5 m/s and southward during the low-water season and <7 m/s and westward during the high-water season. The TSS concentration in the low-water season was higher (>50 mg/L) than that in the high-water season. The TSS concentration during the low-water season was empirically described by wind speed (W), water depth (D), and shear stress (τ_wave) with a function of W3, W3/D, and exp(W/D) or exp(τ_wave), depending on the location in the lake. The critical shear stress due to wind-induced waves at most of the places in the lake was higher than the total shear stress indicated. Sedimentation was predominant in December and June, and erosion (siltation) was dominant in March. Most of the siltation in March was dominant in the southern part of the lake.