Two field experiments were performed on Sakha Agricultural Research Station Farm during 2017/18 and 2018/19 growing seasons, to study the agronomic, physiological, and anatomical response of eleven bread wheat cultivar and lines for two irrigation regimes levels (i.e., five irrigations, (recommended as control) and only one irrigation after 21 days planting (water stress)). Results showed that the agronomic (i.e., number of days to maturity, plant height, grain yield and its components), physiological (i.e., relative water content, and chlorophyll a & b) and anatomocal estimates (i.e., thickness of leaf lamina, cuticle layer, upper epidermis, lower epidermis, mesophyll tissue, midrib, main vascular bundle dimension (length and width), collenchyma tissue, xylem tissue, phloem tissue and bulliform cells) were decreased under water stress conditions, except for proline and leaf temperature. Line 1, Line 2, Sids 14, Giza 171 and Sakha 95 were the most tolerant genotypes and may be suitable for water shortage conditions. High values of relative water content, chlorophyll and proline contents, low values of flag leaf temperature, in addition to the lowest reduction in leaf anatomical characters may be useful selection criteria for water stress tolerance in bread wheat.