Waterlogging stress is one of the greatest environmental threats to kiwifruit growth and development. ERF-VⅡ proteins have been demonstrated to play pivotal roles in regulating plant tolerance to waterlogging. Nevertheless, the genome-wide role of ERF-VⅡ in kiwifruit waterlogging stress tolerance remains unclear. Here, we report the function and regulatory network of an ERF-VⅡ transcription factor located to the nucleus, AvERF73, in kiwifruit waterlogging tolerance. Overexpression of AvERF73 in Arabidopsis thaliana and A. chinensis cv. Hongyang enhanced waterlogging tolerance in transgenic plants. Furthermore, we performed transcriptome analysis (RNA-seq) and DNA affinity purification sequencing (DAP-seq) to explore the regulatory mechanism of AvERF73. RNA-seq coupled with DAP-seq showed that AvERF73 might directly activate AcNAC022 involved in the “cellular response to hypoxia” process and AcHMGS1 involved in the mevalonate pathway to respond to waterlogging, which were also confirmed by a dual-luciferase reporter assay. Based on our results, we propose a putative working model for controlling waterlogging tolerance by AvERF73 in kiwifruit.