Coastal blue carbon storage (CBCS) plays a key role in addressing global climate change and realizing regional carbon neutrality. Although blue carbon has been studied for some years, there is little understanding of the influence of a megacity’s complex natural and human-driven processes on CBCS. Taking the Shanghai coastal area as an example, this study investigated the spatiotemporal change in CBCS using the InVEST (Integrated Valuation of Ecosystem Services and Tradeoffs) model during 1990–2015, and analyzed the response of the CBCS to a megacity’s complex natural- and human-driven processes through a land use/land cover transition matrix and hierarchical clustering. The results were as follows: (1) Thirty-three driving processes were identified in the study area, including four natural processes (e.g., accretion, succession, erosion, etc.), two human processes (reclamation and restoration) and twenty-seven natural–human coupled processes; they were further combined into single and multiple processes with positive and negative influences on the CBCS into four types (Mono+, Mono−, Multiple+ and Multiple− driving processes). (2) Shanghai’s CBCS increased from 1659.44 × 104 Mg to 1789.78 ×104 Mg, though the amount of Shanghai’s coastal carbon sequestration showed a decreasing trend in three periods: 51.28 × 104 Mg in 1990–2000, 42.90 × 104 Mg in 2000–2009 and 36.15 × 104 Mg in 2009–2015, respectively. (3) There were three kinds of spatiotemporal patterns in the CBCS of this study area: high adjacent to the territorial land, low adjacent to the offshore waters in 1990; high in the central part, low in the peripheral areas in 2009 and 2015; and a mixed pattern in 2000. These patterns resulted from the different driving processes present in the different years. This study could serve as a blueprint for restoring and maintaining the CBCS of a megacity, to help mitigate the conflicts between socioeconomic development and the conservation of the CBCS, especially in the Shanghai coastal area.