Soils are highly sensitive to the type of tillage practices used, as these practices influence soil properties and affect crops, the environment, and society. However, research on cassava production under different tillage systems during drought conditions in the Peruvian Amazon has not been reported. The objective of this study was to compare soil properties, cassava physiology, and yield under conservation agriculture (CA) and traditional agriculture (TA) practices, with and without mulch, in a water-scarce environment. Soil moisture, earthworm population (Ew), stomatal conductance, leaf area index, and commercial yield under CA were 5.26% (~105.2 m3 ha−1), 83%, 1.2 times, 1.14 times, and 7.3 t ha−1, respectively, higher than under TA. Hydraulic conductivity (Ks) in TA was 2.1 times higher than that in CA. However, Ks, bulk density, and Ew over time showed a gradual recovery under CA. The mulch factor only affected Ew, which was higher without mulch than with mulch. The results indicate that CA practices were superior to TA practices, improving soil properties, cassava physiology, and yield, and, therefore, offer significant benefits in resource conservation and higher production and profitability in a drought-prone environment.