In the information age, the new wave of the information technology revolution has profoundly changed our mode of production and way of life. Pseudo human settlements (PHS), consisting of digits and information, have become increasingly important in human settlements (HS) systems, and become a strong support for the high-quality development of global HS. Against this background, clarifying the spatiotemporal heterogeneity and driving mechanisms of the coupling and coordination between the PHS and real human settlements (RHS) is of great significance to the high-quality development of HS and providing a reasonable explanation of today’s man–land relationship. Therefore, we developed a theoretical framework system for describing PHS–RHS coupling and coordination based on multi-source data such as internet socialization, public utility, and remote sensing images, etc. Taking the urban agglomeration in the middle reaches of the Yangtze River (UAMRYR), which is the key region consolidating China’s “two horizontal and three vertical” urbanization strategy, as a case study area, we have comprehensively analyzed the spatiotemporal heterogeneity of the coupling and coordination of PHS and RHS and its driving mechanism in UAMRYR during the period of 2011–2021, by comprehensively applying the modified coupling coordination degree (CCD) and other models. The results show are as follows: (1) Temporal process—The CCD exhibited a reverse L-shaped increasing trend. The CCD class varied significantly, with the extremely uncoordinated and severely uncoordinated classes present at the beginning of the study period and disappearing toward the end of the study period, while the well coordinated and highly coordinated classes were absent at the beginning of the study period and appeared toward the end of the study period. (2) Spatial pattern—The CCD exhibited an equilateral triangle-shaped, core–margin spatial pattern and a characteristic of core polarization. Overall, the spatial distribution of the CCD exhibited a characteristic of “high in the central region, low in the eastern and western regions, and balanced in the south–north direction”. (3) Dynamic evolution—The CCD increased more rapidly in the north-eastern direction than in the south-western direction; the CCD exhibited north-eastward migration and dispersion, and the spatial variability decreased. (4) Driving mechanisms—The primary factors affecting the CCD varied significantly over time. The living system was dominant in the PHS, whereas the human system was dominant in the RHS. The PHS had a greater effect than the RHS on the CCD. The study broadens the research scope of human settlements geography, establishes a scientific foundation for advancing urban HS construction in the UAMRYR, and offers theoretical support for the high-quality development of cities in the UAMRYR.