The fouling of seawater reverse osmosis (SWRO) membranes remains a persistent challenge in desalination. Previous research has focused mainly on fouling separately; however, organic, inorganic, and biofouling can coexist and influence each other. Hence, in-depth study of the spatiotemporal changes in actual combined fouling in full-scale seawater desalination will provide more effective information for fouling investigation and control. In this study, we monitored (i) the operational performance of a full-scale desalination plant for 7 years and (ii) the development and characterization of membrane and spacer fouling at different locations of spiral-wound membrane modules sampled after 2.5-, 3.5-, and 7-year operation. The findings showed that (i) operational performance indicators declined with time (normalized flux 40 % reduction, salt rejection 2 % in 7 years), with a limited effect of the 20-day cleaning frequency, (ii) fouling accumulation in the membrane module mainly occurred at the feed side of the lead module and the microbial community in these area exhibited the highest diversity, (iii) the dominant microbial OTUs belonged mainly to Proteobacteria (43-70 %), followed by Bacteroidetes (10-11 %), (iv) Phylogenetic molecular ecological networks and Spearman correlation analysis revealed that Chloroflexi (Anaerolineae) and Planctomycetes were keystone species in maintaining the community structure and biofilm maturation and significantly impacted the foulant content on the SWRO membrane, even with low abundance, and that (v) fouling accumulation was composed of polysaccharides, soluble microbial products, marine humic acid-like substances, and inorganic Ca/Fe/Mg/Si dominate the fouling layer of both the membrane and spacer. Overall, variation partitioning analysis quantitatively describes the increasing contribution of biofouling over time. Ultimately, the organic‒inorganic-biofouling interaction (70 %) significantly contributed to the overall fouling of the membrane after 7 years of operation. These results can be used to develop more targeted fouling control strategies to optimize SWRO desalination plant design and operation.