Due to an extreme increase in population growth, Egypt suffers from a widening gap in the quantity of imported wheat compared with production and local consumption. Two field trials were conducted during the 2018/2019 and 2019/2020 seasons with three levels of humic substances (HSs) as a foliar spray (1.0, 2.0 and 4.0 g L−1; HS1, HS2 and HS3) and three levels (5.04, 7.56 and 10.08 kg ha−1; HS4, HS5 and HS6) as a soil application. These were applied three times (30, 45 and 60 days after sowing) in comparison with the control (HS0) to evaluate the performance of three wheat varieties (Seds1 (V1), Misr2 (V2) and Giza168 (V3)) grown in clay loam soil. The experiment was set up according to the split-plot structure in a randomized complete block design; however, the varieties were set as the main plot and treatments were a sub-main plot. Generally, the data indicated that the soil application treatments recorded maximum values for most growth and yield attributes, except for spike length and grain weight per spike, SPAD reading and total grain yield in the first season, and leaf area and biological yield in the second season. HS1, HS2, HS5, and HS6 were the superior treatments for most of the nutrient contents studied. Regarding the influence of variety, the results showed that V3 recorded maximum values for LA, SpL, TGW, TGY and leaf Zn and Cu contents in both seasons; PH, GWS and leaf N content in the first season; and SPAD reading, BY and leaf K, Fe and Mn contents in the second season. V1 was the superior variety for GWS, BY, leaf K and Mn contents in the 2018/2019 season and PH, GNS in the second season, followed by V2, which had the greatest values for leaf P contents in both seasons, and SPAD reading, GNS and leaf Fe content in the 2018/2019 season and GWS and leaf N content in the second season.