Abstract: This study was conducted to investigate black sigatoka disease and drought stress responses of off-type plants derived from shoot-tip micropropagation of East African highland banana (Musa AAA East Africa) landrace Uganda. Results showed that the off-type plants were more (p<0.05) tolerant to black sigatoka disease with the infection index of 17.5% compared to 30.1 and 22.8% of the micropropagation (MP) derived phenotypically normal plants and Conventional Propagation (CP) derived plants with no tissue culture history in their ancestry, respectively. On the contrary, the off-type plants were more (p<0.05) vulnerable to water stress with leaf senescence of 87.7% at soil water deficit of 630 millibars. The leaf senescence of the MP and CP derived plants at the same soil moisture deficit was 79.5 and 66.7%, respectively. During this stress period each off-type plant produced one sucker, while the true-to-type plants were unable to do so. Leaf structural analysis revealed that the off-type plants had higher (p<0.05) stomatal density of 16.0 mm-2 of the upper leaf surface. Conversely, the MP and CP derived plants had each 12.3 and 11.0 stomata mm-2 of the leaf upper surface. Similarly, the off-type plant leaves were more hydrophobic with higher (p<0.05) epicuticular waxiness of 684.6 μg cm-2. The epicuticular wax content of the MP and CP derived plant leaves was as low as 646.2 and 647.7 μg cm-2, respectively. The water stressed off-type plant leaves exhibited higher (p<0.05) membrane damage with ion leakage of 168.2 μS cm-1 compared to 139.7 and 136.8 μS cm-1 of the MP and CP derived plants. Moreover, the water stressed leaves of the off-type plants had enhanced total antioxidant activity of 5.17 M trolox equivalent per milligram proteins, whereas the total antioxidant activity of the MP and CP derived plant leaves was as low as 3.76 and 3.67 M trolox equivalent per milligram proteins, respectively.