Selenium (Se) and silicon (Si) are considered advantageous elements to induce plants’ tolerance to various environmental stresses. Wheat yield is negatively affected by salinity stress, especially in dry and semi-dry areas. Therefore, the objective of the current study was to investigate the effects of Se, Si and their combinations (0 as control, Se15, Se30, Si15, Si30, Se15 + Si15, and Se30 + Si30 mM) in alleviating the deleterious effects of salinity stress (7.61 dS m−1, real field conditions) on anatomical characteristics as well as the physio-biochemical and productivity parameters of wheat plants. The selenium and silicon treatments and their combinations caused significant amelioration in growth, anatomical and physiological attributes, and grain yields of salinity-stressed wheat in comparison with the untreated plants (control treatment). The integrated application of Se30 + Si30 significantly increased plant growth (i.e., plant height 28.24%, number of tillers m−2 76.81%, fresh weight plant−1 80.66%, and dry weight plant−1 79.65%), Fv/Fm (44.78%), performance index (PI; 60.45%), membrane stability index (MSI; 36.39%), relative water content (RWC; 29.39%), total soluble sugars (TSS; 53.38%), proline (33.74%), enzymatic antioxidants (i.e., CAT activity by 14.45%, GR activity by 67.5%, SOD activity by 35.37% and APX activity by 39.25%) and non-enzymatic antioxidants (i.e., GSH content by 117.5%, AsA content by 52.32%), yield and its components (i.e., number of spikelets spike−1 29.55%, 1000-grain weight 48.73% and grain yield ha−1 26.44%). The anatomical traits of stem and leaves were improved in wheat plants treated with Se30 + Si30. These changes resulting from the exogenous applications of Se, Si or their combinations, in turn, make these elements prospective in helping wheat plants to acclimate successfully to saline soil.