Unprecedented large-scale harmful algae blooms (HABs) were reported in coastal waters off the south-eastern coast of Hokkaido, Japan, in mid-to-late September 2021, about a month after very intense and extensive marine heatwaves subsided. To understand the physical–biological processes associated with development of the HABs, we conducted analyses via a combination of realistic ocean circulation models, particle-tracking simulations, and satellite measurements. The satellite-derived chlorophyll concentrations (SCCs) and areal extent of the high SCCs associated with the HABs were the highest recorded since 1998. More specifically, the extent of SCCs exceeding 5 or 10 mg m−3 started to slowly increase after 20 August, when the marine heatwaves subsided, intermittently exceeded the climatological daily maximum after late August, and reached record-breaking extremes in mid-to-late September. About 70% of the SCCs that exceeded 10 mg m−3 occurred in places where water depths were <300 m, i.e., coastal shelf waters. The high SCCs were also tightly linked with low-salinity water (e.g., subarctic Oyashio and river-influenced waters). High-salinity subtropical water (e.g., Soya Warm Current water) appeared to suppress the occurrence of HABs. The expansion of the area of high SCCs seemed to be synchronized with the deepening of surface mixed layer depths in subarctic waters on the Pacific shelves. That deepening began around 10 August, when the marine heatwaves weakened abruptly. However, another mechanism was needed to explain the intensification of the SCCs in very nearshore waters off southeast Hokkaido. Particle-tracking simulations based on ocean circulation models identified three potential source areas of the HABs: the Pacific Ocean east of the Kamchatka Peninsula, the Sea of Japan, and the Sea of Okhotsk east of the Sakhalin Island. Different processes of HAB development were proposed because distance, time, and probability for transport of harmful algae from the potential source areas to the study region differed greatly between the three source areas.