Irregular rainfall distribution has increased incidences of mid-season drought in Western Kenya despite high amount of annual rainfall. This experiment’s aim was to determine soil moisture content under soybean and grain yield during midseason drought. The objective was evaluated at two agro-ecological zones using sowing dates as main-plots, conventional and no tillage as sub-plots and Nyala, SB19 and SB20, soybean varieties, as sub-sub-plots. Soil moisture content between tillage methods at R2 and R4 in long and short rains were similar in Kanduyi and Alupe. However, it was different between sowing dates, among varieties and among interactions. Soybean grain yield was high on sowing at two weeks after the onset of long and short rains in Kanduyi whereas in Alupe it was the contrary. Increases of 5.9% and 12.8% in soil moisture in long rains and short rains respectively at R2 led to grain yield gain of 47.8% and 27.2% respectively at Kanduyi. Therefore, sowing at the onset of rains in Alupe and at two weeks after the onset of rains in Kanduyi increases soil moisture at R2 and R4 and consequently mitigates mid-season drought.