The Northwest Pacific Ocean (NWP) is one of the most vulnerable regions that has been hit by typhoons. In September 2018, Mangkhut was the 22nd Tropical Cyclone (TC) over the NWP regions (so, the event was numbered as 1822). In this paper, we investigated the highest amplitude ionospheric variations, along with the atmospheric anomalies, such as the sea-level pressure, Mangkhut’s cloud system, and the meridional and zonal wind during the typhoon. Regional Ionosphere Maps (RIMs) were created through the Hong Kong Continuously Operating Reference Stations (HKCORS) and International GNSS Service (IGS) data around the area of Mangkhut typhoon. RIMs were utilized to analyze the ionospheric Total Electron Content (TEC) response over the maximum wind speed points (maximum spots) under the meticulous observations of the solar-terrestrial environment and geomagnetic storm indices. Ionospheric vertical TEC (VTEC) time sequences over the maximum spots are detected by three methods: interquartile range method (IQR), enhanced average difference (EAD), and range of ten days (RTD) during the super typhoon Mangkhut. The research findings indicated significant ionospheric variations over the maximum spots during this powerful tropical cyclone within a few hours before the extreme wind speed. Moreover, the ionosphere showed a positive response where the maximum VTEC amplitude variations coincided with the cyclone rainbands or typhoon edges rather than the center of the storm. The sea-level pressure tends to decrease around the typhoon periphery, and the highest ionospheric VTEC amplitude was observed when the low-pressure cell covers the largest area. The possible mechanism of the ionospheric response is based on strong convective cells that create the gravity waves over tropical cyclones. Moreover, the critical change state in the meridional wind happened on the same day of maximum ionospheric variations on the 256th day of the year (DOY 256). This comprehensive analysis suggests that the meridional winds and their resulting waves may contribute in one way or another to upper atmosphere-ionosphere coupling.