Agronomic practices have a large effect on the yield and profitability of low-input smallholder cotton farming in Africa. A two-season field experiment was conducted in a semi-arid cotton growing area in Meatu District, Tanzania, to compare the yield and profitability of various conventional and organic cotton production practices. Besides the currently applied low-input conventional and organic cotton production practices, higher-input and innovative farming practices as well as control treatments (without fertiliser or pesticides) were tested. While season 1 had weather conditions that were very suitable for cotton production, much less rainfall in season 2 severely reduced the yield and land rent in both conventional and organic cotton production. In general, conventional and organic practices have similar cotton yields, but organic practices often generate higher land rents than conventional practices due to a higher price for organic cotton and lower production costs. In both seasons, the innovative organic practice generated the highest land rent of all conventional and organic practices, and it is statistically significantly higher than the land rents of all conventional farming practices.