Cotton (Gossypium hirsutum L.) is one of the top economic crops in South Carolina, and growers make many important decisions prior to planting each year including variety selection, planting date, seed size, and seeding rate. As input costs continue to rise, greater detailed information is needed so that growers can make better informed decisions for their individual operations. The objectives of this study were to evaluate the influence of seed size, seeding rate, and planting date on the growth, development, lint yield, and fiber quality for cotton grown in South Carolina. Two seed sizes large (≤9460 seed kg−1) and small (≥12,100 seed kg−1) were planted at four seeding rates (61,775; 86,485; 111,195; and 135,905 seeds ha−1) on two different planting dates (early [late April/early May] and late [late May/early June]) in 2020, 2021, and 2022 in Florence and in 2020 and 2021 in Blackville, SC. Data collection included stand counts, biomass at multiple growth stages, plant height, lint yield, fiber quality, and overall net returns. Results showed no difference in lint yield for any of the factors in either location in 2020; however, the small‐seeded variety lint yield was 20% more than the large‐seeded variety in Florence in 2021 and 2022 and 5% higher in Blackville in 2021. In Florence, seeding rates over 100,000 seed ha−1 resulted in higher lint yield than the lower two seeding rates. In both locations, delaying planting until after May 22 increased lint yield by approximately 15% in 2021 and 2022. The large‐seeded variety consistently had greater dry biomass (12%–52% greater) than the small‐seeded variety, indicating that it produced larger, more vigorous seedlings. While seed size may not be a reliable predictor of lint yield, it has proven to be an accurate predictor of seedling vigor. Therefore, it may be beneficial to plant a high‐yielding, larger seed size variety when unfavorable planting conditions are expected.