Seed size, sowing depth, and seed disinfection can affect seed germination and seedling establishment, which, in turn, can directly affect crop growth and yield. The current study was comprised of two experiments, the first of which was conducted in the laboratory, and a second which was performed under glasshouse conditions. The objective of these experiments was to investigate the effects of seed size, sowing depth, and seed disinfection on seed germination and initial seedling growth of selected wheat (Triticum aestivum L.) cultivars. The treatments in laboratory experiment were arranged in a completely randomized design, which included: (Ι) four wheat cultivars (Pishgam, Haydari, Soissons, and Mihan), (ΙΙ) two seed size classes (x < 2.25 mm, and x > 2.25 mm), and two disinfection treatments (no-disinfection and disinfection), (ΙΙΙ) with five replicates. In addition to the aforementioned treatments, the effect of planting depth (4, 6, and 8 cm) was also investigated in the subsequent glasshouse experiment. The best results were obtained at a sowing depth of 4 cm, in the non-disinfected treatment, using large seeds. In contrast, the lowest percentage and speed of seed germination and vigor index were observed in seeds sown at 8 cm depth, in the disinfected seed treatment, using small seeds. Large seeds contain larger nutrient stores which may improve seed germination indices, which would therefore result in improved percentage and speed of seed germination, followed by faster coleoptile and seedling growth, higher seedling dry weight and seed vigor. These data also illustrated that seed disinfection in the Pishgam and Haydari cultivars had inhibitory effects upon coleoptile growth and seedling length, which could be related to the fungicide’s chemical composition. Unlike other cultivars, disinfection did not show a significant effect on the Soissons cultivar. Based on our data, in order to improve both the speed of wheat seed germination and subsequent plant growth and development; it is necessary to select high-quality, large seeds, planted at a specific planting depth, which have been treated with an effective disinfectant; all of which will be specific for the wheat cultivar in question. Overall, the current study has provided useful information on the effect size seed, sowing depth, and disinfection have upon germination characteristics and seedling growth of wheat cultivars, which can form the basis for future field scale trails.