M. laxiflora is an endangered plant that grows in the Yangtze River floodplain of China and often suffers from flooding stress. Due to the lack of a reference genome for M. laxiflora, the molecular regulatory mechanism of waterlogging stress in this plant remains unclear. In this study, we report a high-quality reference genome of M. laxiflora with a size of 1.29 Gb. A total of 23,666 gene-encoding proteins and 5457 ncRNAs were predicted in this reference genome. A comparative genome analysis revealed that 902 and 4299 gene families significantly expanded and contracted, respectively, in M. laxiflora. The expansions of the 902 gene families were significantly related to the “response to stress”, “response to abiotic stimulus”, and “response to oxygen-containing compounds” pathways. In the M. laxiflora genome, 101 MylAP2/ERF genes were identified and divided into five subgroups. Several MeJA-, ABA-, and hypoxia-responsive elements were found in the promoter regions of these MylAP2/ERF genes. According to the transcriptome data analysis, 74 MylAP2/ERF genes responded to flooding stress. Moreover, three genes (MylAP2/ERF49/78/91) that belong to the same branch as the RAP2.2 gene exhibited different expression trends under flooding stress. Our results provide valuable information on the molecular regulatory mechanism of flooding stress in M. laxiflora.