The rapidly developing urbanization since the last decade of the 20th century has led to extensive groundwater extraction, resulting in subsidence in Ho Chi Minh City, Vietnam. Recent advances in multi-temporal spaceborne SAR interferometry, especially with a persistent scatters interferometry (PSI) approach, has made this a robust remote sensing technique for measuring large-scale ground subsidence with millimetric accuracy. This work has presented an advanced PSI analysis, to provide an unprecedented spatial extent and continuous temporal coverage of the subsidence in Ho Chi Minh City from 2006 to 2010. The study shows that subsidence is most severe in the Holocene silt loam areas along the Sai Gon River and in the southwest of the city. The groundwater extraction resulting from urbanization and urban growth is mainly responsible for the subsidence. Subsidence in turn leads to more flooding and water nuisance. The correlation between the reference leveling velocity and the estimated PSI result is R2 = 0.88, and the root mean square error is 4.3 (mm/year), confirming their good agreement. From 2006 to 2010, the estimation of the average subsidence rate is -8.0 mm/year, with the maximum value up to -70 mm/year. After four years, in regions along Sai Gon River and in the southwest of the city, the land has sunk up to -12 cm. If not addressed, subsidence leads to the increase of inundation, both in frequency and spatial extent. Finally, regarding climate change, the effects of subsidence should be considered as appreciably greater than those resulting from rising sea level. It is essential to consider these two factors, because the city is inhabited by more than 7.5 million people, where subsidence directly impacts urban structures and infrastructure.