Tomato cultivars (Heinz 1370, MT 56, and Nuru F1), fungicide application (±), staking (±), and mulching (±) were tested for their effect on yield, disease severity, and gross margin in tomato production in the Kamuli District of Uganda. Treatments were arranged in a randomized complete block design with a factorial and split-plot arrangement in field plots in two growing seasons during 2013. Total and marketable fruit number, marketable fruit weight, gross margin, and disease severity, assessed using the area under disease progress curve, were measured. Disease-resistant and open-pollinated ‘MT 56’ in combination with fungicide application and soil mulch provided the highest marketable fruit number and marketable fruit weight and had a positive gross margin in the first growing season. A combination of ‘MT 56’ and treatments without applying fungicide and soil mulch resulted in the only positive gross margin in season two. Application of fungicides reduced disease severity (early blight, Alternaria solani Sorauer) for all cultivars in season one and for ‘Heinz 1370’ and ‘Nuru F1’ in season two, but did not affect disease severity for ‘MT 56’ in the second season. Using soil mulch reduced the severity of early blight disease, but decreased the gross margin when purchased. Staking did not affect yield, disease severity of plants, and decreased the gross margin. Cultivar MT 56 had the highest gross margin and marketable fruit and least disease severity, and seeds should be made available to small-landholder tomato farmers in Uganda to enhance their sustainable livelihoods.