The current study was carried out at the experimental farm of Rice Research Department, Sakha Agricultural Research Station and Central Agricultural Pesticide Laboratory, ARC, Egypt during the summer season of 2021 and 2022 to study the sensitivity of three Egyptian rice cultivars against four common herbicides and its effect on physiological and agronomic characteristics of rice as well as herbicide residues in rice seeds. The field study was laid out in split plot design with three replications. Three rice cultivars (Giza 177, Giza 179 and Sakha 108) were randomly distributed in main plots, while weed control treatments included four herbicides at recommended doses (penoxsulam 2.5% OD, bispyribac-sodium 2% SL, cyhalofop-butyl 10% EC and fenoxaprop-p-ethyl 7.5% EW) as compared to hand weeding were devoted in sub plots. The obtained results revealed that Sakha 108 as Japonica rice cultivar was resistant against tested herbicides and recorded the highest values of rice dry weight, chlorophyll content, number of panicles m-2, panicle weight and grain yield, while scored the lowest values of total phenols. On the other hand, Giza 177 as short duration Japonica rice cultivar showed the higher sensitivity against tested herbicides and achieved the lowest values of abovementioned agronomic traits and chlorophyll content. Cyhalofop-butyl as ACCase herbicide was safer on studied rice cultivars and recorded the highest values of studied agronomic characteristics for rice as well as chlorophyll content, while recorded the lowest values of total phenols during the study. On the other hand, bispyribac-sodium 2% SL resulted in more toxic effect for rice cultivars and recorded the lowest values of studied agronomic traits for rice. fenoxaprop-p-ethyl 7.5% EW achieved the lowest chlorophyll content and highest values of total phenols during the study. Giza 179 as Indica-Japonica rice cultivar appeared high sensitivity when sprayed with bispyribac-sodium and fenoxaprop-ethyl but made recovery after 12 days from herbicidal application and recorded the highest chlorophyll content, dry weight, panicles m-2 and grain yield with no significant differences between Sakha 108 rice cultivar during the study. In respect of herbicide residues in rice seeds, all tested herbicides didn’t have residues in rice seeds at 100 days after treatment. It means that tested herbicides didn’t have any residues in rice seeds.