Little is known about how cropping systems influence soil quality and fertility in Uganda. Some cropping systems are more valued and as a result are given more nutrients and planted in certain soils, all of which leads to varying soil quality and fertility. This study compared soil quality (soil pH, cation exchange capacity (CEC), electric conductivity (EC), total N, and depth to restrictive layer (DRL)) and fertility (extractable P, K, Ca, Mg, and Na, and base saturation (BS) from five cropping systems (banana (Musa × paradisiaca L.)-dominant (B), coffee [Coffea robusta (L.) Linden]-dominant (C), banana-coffee (BC), annual with no crop rotation (ANR), and annual with crop rotation (AR); fertilized and unfertilized soils; and three soil types (black (Phaeozem), red (Ferralsol), and black-stony) in south-central Uganda. The analysis included farm assessments to establish management history of studied fields and soil sampling from 52 fields in Masaka District, Uganda. Main-effects ANOVA was employed to determine differences in means in soil under different cropping systems, soil types, and fertilizer use. Soil quality (pH at depths of 0 to 10 and 20 to 30 cm, CEC, and EC) and fertility (extractable Ca and Mg) varied by cropping system. The AR and B systems had higher soil quality and fertility compared to other cropping systems. Soil quality (pH at depths of 0 to 10 and 0 to 15 cm and DRL) and soil fertility (extractable P and K) varied by soil type. Black and black-stony soils had higher soil quality and fertility than red soils. Soil quality and fertility did not vary by fertilizer use. The results of this study indicate that both cropping system and soil type are associated with soil quality and fertility in south-central Uganda.