Sweet potato (Ipomoea batatas L.), typically cultivated in temperate climates under low inputs, is one of the most important crops worldwide. Abscisic acid (ABA) is an important plant stress-induced phytohormone. Hitherto, few works analyzed the ABA function in sweet potato tissue growth. Very scarce information is available concerning the ABA role in sweet potato response to water scarcity conditions. Here, we show the ABA content variation in shoots and tubers of eight sweet potato accessions subjected to drought stress. ABA was also related to other resistance traits, such as chlorophyll content index (CCI), carbon isotopic discrimination (¿13C), oxalic acid (OA) and water use efficiency (WUE), to assess stress response mechanisms to water deficit between their organs. The most resilient drought-stressed sweet potato plants accumulated ABA-shoot, and significantly decreased the ABA-tuber content. ABA signaling was related to ¿13C and CCI decrease and WUE increment, as an attempt to cope with water stress by partially closing the stomata. The partial closure of stomata could be in part due to the presence of OA-shoots, known to affect the intensity of the ABA-shoot signal in stomatal closure. Higher CCI content and minimal ¿13C-shoot differences indicated good carboxylation fractionation, with higher ¿13C-tuber content as an indicator of efficient tuber 13C fixation and growth. Our work demonstrated that ABA could be used in conjunction with the other traits studied for the assessment of sweet potato whole-plant responses to environmental stresses, and thus aid the selection of the best drought tolerant genotypes for breeding programs.