Built-up land in floodplains (BLF) is a driver and a disaster-bearing body of flood risk from a socio-hydrological perspective. The relationship between BLF growth and flood vulnerability is the key to understanding and managing flood risk. However, previous studies have focused more on the relationship between BLF growth and flood exposure, ignoring flood vulnerability. We examined the BLF expansion pattern (patch size and expansion type) in the North China Plain Area from 1975 to 2014 (1975–1990–2000–2014) using GIS (geographic information system)-based landscape analysis and revealed its relationship with flood vulnerability. The results show that the BLF area experienced rapid growth (288.26%) from dispersion to coalescence. Small patches dominated the number and area of BLF growth, and edge-expansion patches were the expansion type with the most area growth. We discovered that flood vulnerability was significantly correlated with the growth in small (R = 0.36, p < 0.01), edge-expansion (R = 0.53, p < 0.01), and outlying patches (R = 0.51, p < 0.01). Large patches were not significantly correlated with flood vulnerability (R = 0.18, p > 0.1), but there was a negative trend. Infilling patch growth was significantly associated with flood vulnerability over a long period (R = 0.27, p < 0.05). In addition, we suggest nature-based soft adaptations or village merging for small patches and outlying patches. Our findings have important scientific significance for adequately understanding the interplay between BLF growth and flood risk. It has practical implications for the formulation of integrated flood risk management strategy and the sustainable development of floodplains.