This paper presents the methodology used to detect temporal changes in the extent of annual flooding within the Cambodia and the Vietnamese Mekong Delta (VMD) based on MODIS time-series imagery (Wavelet-based Filter for detecting spatio-temporal changes in Flood Inundation; WFFI). This methodology involves the use of a wavelet-based filter to interpolate missing information and reduce the noise component in the time-series data, as proposed in a previous study. The smoothed time profiles of Enhanced Vegetation Index (EVI), Land Surface Water Index (LSWI), and the Difference Value between EVI and LSWI (DVEL) are obtained from MOD09 8-day composite time-series data (resolution: 500 m; time period: 2000–2005). The proposed algorithm was applied to produce time-series inundation maps (WFFI products) for the five annual flood seasons over the period from 2000 to 2004. The WFFI products were validated via comparisons with Landsat-derived results and inundation maps based on RADARSAT images, hydrological data, and digital elevation model data. Compared with the RADARSAT-derived inundation maps at the province level, the obtained RMSE range from 364 to 443 km 2 and the determination coefficients [ R 2] range from 0.89 to 0.92. Compared with Landsat-derived results at the 10-km grid level, the obtained RMSE range from 6.8 to 15.2 km 2 and the determination coefficients [ R 2] range from 0.77 to 0.97. The inundated area of flooded forests/marsh to the northeast of Tonle Sap Lake were underestimated, probably because of extensive vegetation cover in this area. The spatial characteristics of the estimated start dates, end dates, and duration of inundation cycles were also determined for the period from 2000 to 2004. There are clear contrasts in the distribution of the estimated end dates and duration of inundation cycles between large-scale floods (2000–2002) and medium- and small-scale floods (2003 and 2004). At the regional scale, the estimated start dates for the southern part of An Giang Province during 2003 and 2004 was distinctly later than that for surrounding areas. The results indicate that these triple-cropping areas enclosed by dikes increased in extent from 2003 to 2004. In contrast, the estimated end dates of inundation at the Co Do and Song Hau State Farms were clearly earlier than those for surrounding areas, although the estimated start dates were similar. Temporal changes in the inundation area of Flood pixels in the Dong Thap and Long An Provinces are in excellent agreement with daily water-level data recorded at Tan Chau Station. The estimated area of Long-term water body increased in size from 2000 to 2004, especially in coastal areas of the Ca Mau and Bac Lieu Provinces. Statistical data for Vietnam indicate that this trend may reflect the expansion of shrimp-farming areas. The WFFI products enable an understanding of seasonal and annual changes in the water distribution and environment of the Cambodia and the VMD from a global viewpoint.