Southern China (SC) is often subjected to the impacts of extreme heat-wave (EHW) events with hot days covering large areas and lasting extended periods in the boreal summer. The present study explores new objective identification methods of the EHW events and reveals the controlling factors of different spatial-temporal variations in shaping the EHW events over SC from 2000 to 2017 with in-situ observations and latest reanalysis. A compound index of the EHW (with impact area, duration, and magnitude) was defined to quantify the overall intensity of the EHW events in SC. It was found that synoptic variability and 10–30-day intra-seasonal variability (ISV) induce the onsets of the EHW events, while 30–90-day ISV shapes the durations. An innovative daily compound index was introduced to track the outbreak of the EHW events. The occurrences of the EHW in SC are coincident with the arrivals of intra-seasonal signals (e.g., the anomalies of outgoing long-wave radiation (OLR) and 500 hPa geopotential height) propagating from the east and south. About 12 days before the onset of the EHW in SC, the 10–30-day positive anomalies of 500 hPa geopotential height and OLR appear near the equatorial western Pacific, which then propagate northwestward to initiate the EHW in SC. At the same time, the 30–90-day suppressed phase propagates northeastward from the Indian Ocean to the SC to sustain the EHW events. On the interannual time scale, it was found that the EHW events in SC occurred in those years with robust warming of the western North Pacific in early summer (May and June) and warming of the equatorial eastern Pacific in the preceding winter (December, January, and February). An interannual sea surface temperature anomalous (SSTA) index, which adds together the SSTA over the above two regions, serves as a very useful seasonal predictor for the EHW occurrences in SC at least one-month ahead.