The systemic fungicides tricyclazole (Beam 75% WP) and isoprothiolane (Fuji-one 40% EC) are widely used to control Pyricularia oryzae infection causing rice blast disease in Egypt. A field experiment was conducted at Rice Research and Training Center farm, Sakha, Kafrelsheikh, Egypt during 2015 and 2016 seasons on susceptible cultivar  Sakha 101. The impact of tricyclazole (0.5 mg/L) and isoprothiolane (2 ml/L) on P. oryzae infection, yield and its components, grain quality and chemical components of rice were evaluated. Meanwhile, the fungicides residue dynamics on rice straw, husk and milled rice were determined using Quick Easy Cheap Effective Rugged and Safe (QuEChERS) method combined with HPLC-MS/MS detection after 30 and 60 days post-harvest. The results indicated that tricyclazole and isoprothiolane were significantly possessed a high level of controlling blast disease whereas, both fungicides reduced disease severity, areas under disease progress curve (AUDPC), and rate of leaf blast progress (r-value) disease parameters in both seasons. Residue analysis of tricyclazole in rice straw (1.06 mg/kg) was higher than the residue in the husk and milled rice (0.19 and 0.14 mg/kg, respectively) after 30 days post-harvest. The residues of tricyclazole in the husk and milled rice were lower than the Maximum Residue Limit (MRL). Also, isoprothiolane residue analysis in milled rice was 0.58 mg/kg after 60 days post-harvest and below the MRL. Also, most of the yield and yield components were significantly increased by the application of both fungicides over the untreated plots. Tricyclazole and isoprothiolane treatments enhanced the grain chemical components concentration as carbohydrates, fats, ash, and fiber. Finally, the investigation revealed that tricyclazole and isoprothiolane were effective against rice blast disease and considered safe fungicides according to the European Food Safety Authority. Based on our residue analysis results and Egyptian rice consumption, we suggested that determine our own Egyptian MRL. Whereas, our total rice consumption reaching 4 million ton/year in 2016, it was considered fourth fold than Europe consumption (1 million ton/year).