Flooding stress, including waterlogging and submerge, is one of the major abiotic stresses that seriously affect growth and development of plants. Epigenetic modifications, such as histone methylations and DNA methylation, their potential regulation in response to flooding stress, remain largely unclear. In the present study, the physiological, epigenetic and transcriptomic analysis were investigated in wheat seedlings under surface-submerge (SS), half-submerge (HS) and full-submerge (FS) treatments. The results demonstrated that significant physiological changes were observed, and different changes were also detected among the three flooding treatments, such as, FS induced higher level of hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents and higher reduction in chlorophyll contents (SPAD), photosynthetic efficiency (Fv/Fm) and shoots dry weight than that of HS and SS. HS induced a higher superoxide dismutase (SOD) and catalase (CAT) activities than that of FS and SS. There was no significant difference between SS and HS in the reduction of shoot dry weight and SPAD value. The acetylation levels of histones H3K9 and tri-methylation level of histone H3K4 were significantly increased, whereas the tri-methylation level of histone H3K27 was decreased in the seedling leaves exposed to flooding stress compared with the control seedlings. DNA methylation level was increased under SS and HS, and decreased under FS. A total of 9,996, 10,619 and 24,949 genes were differentially expressed under SS, HS, and FS treatments, respectively, among which ‘phenylpropanoid biosynthesis’ and ‘plant hormone signal transduction pathways were extensively enriched in the three flooding treatments, these genes showed flooding-type specific expression. Moreover, flooding type specific responses were observed among the three conditions, including specific TFs and response pathways. These results will contribute a better understanding of the molecular mechanisms of wheat seedling leaf responses to flooding stress and provide valuable genetic and epigenetic information for breeding flooding tolerant varieties of wheat.