Vegetation coverage in coastal wetlands has been significantly altered in response to multiple disturbances over recent decades. However, the major driving factor of vegetation coverage in coastal wetlands remains unclear, with natural and human factors playing interactive roles at the national scale. To identify the major controls of vegetation coverage in coastal wetlands, structural equation modeling (SEM) was conducted to quantify the relative contribution of natural and human factors to vegetation coverage in coastal wetlands in China over a 16-year period (2000–2015). The results showed that, in brief, vegetation coverage was slightly degraded (k = −0.0035) over the 2000–2015 period. The area with a probability of vegetation coverage degeneration ≥80% covered 16.6% of the study area. Most annual mean vegetation coverage was lower but improved near the sea, with inverse results obtained near land. In 2000, human1 (population and GDP, r = −0.31) and topography (r = 0.32) were the major controls of vegetation coverage. The vegetation coverage (2000) played the most important and positive role (r = 0.62, r = 0.66) in the vegetation coverage in 2015. Our findings highlight that the major drivers of vegetation coverage in coastal wetlands changed with time and selected variables.