The phytohormone abscisic acid (ABA) is important during abiotic stresses, especially drought stress. Although mitogen-activated protein kinase (MAPK) cascades are crucial for ABA-mediated drought tolerance, how these cascades integrate and deliver the downstream ABA signals is poorly understood. Here, the group C MAPK GhMPK7 was found to positively regulate ABA-mediated drought tolerance in cotton. Silencing GhMPK7 decreased drought tolerance in transgenic cotton plants. After ABA treatment, the GhMPK7-silenced transgenic plants were not sensitive to ABA, exhibited restricted stomatal closure, faster germination rates and longer roots. Importantly, GhSDIRIP1, a negative regulator of ABA signaling, was found to interact with GhMPK7 as a downstream. Silencing GhSDIRIP1 in GhMPK7-silenced transgenic cotton plants restored the drought-intolerant phenotype caused by GhMPK7 silencing. The results of the phosphorylation experiments revealed that GhMPK7 can phosphorylate the Ser-19 residue of GhSDIRIP1 to regulate its stability. GhMPK7-induced GhSDIRIP1 protein degradation increased ABA signaling intensity in response to drought stress. Overall, our findings provide insights into the positive regulatory mechanism of ABA-involved drought tolerance, which is mediated by the GhMPK7-GhSDIRIP1 module. This study expands our knowledge of how MAPK cascades regulate the intensity of ABA-mediated drought tolerance in plants and advances our understanding of the interplay between phosphorylation and ubiquitination.