The present study aimed to determine differences in drought tolerance between three widely-cultivated soybean cultivars in Egypt. Two field experiments were conducted at the experimental farm and laboratories of the Agric. Bot. Dept., Fac. of Agric., Mansoura Univ., Egypt during the two growing seasons of 2013 and 2014. The experimental design was a split-plot with two irrigation regimes in the main plots (control and water stress) and three cultivars in the sub-plots (Giza 22, Giza 35 and Giza 111).  Results indicated that drought stress decreased seed yield, dry biomass, relative growth rate (RGR), net assimilation rate (NAR), relative water content (RWC), membrane stability index (MSI), whereas increased phenols, flavonoids, anthocyanins and proline content differentially between the tested cultivars. Drought tolerance index of cv. Giza 111 was significantly higher than other studied cultivars and this was accompanied with higher biomass accumulation, RGR, NAR, RWC, MSI as well as higher content of phenols, flavonoids, anthocyanins and proline. It was concluded that cv Giza 111 is better-adapted to drought-affected areas and could be utilized in breeding programs aiming to increase drought tolerance in soybean.