A widespread opinion appears to prevail that the two recent deadly Mexico earthquakes, i.e., M8.2 on 7 September 2017 and M7.1 on 19 September 2017, in Chiapas and Morelos regions, respectively, had an unusual cause. Here, upon considering the analysis of seismicity in the new time domain termed natural time, we show that the occurrence of the M8.2 earthquake, which is Mexico’s largest earthquake in more than a century, should not be considered unexpected. In particular, this analysis revealed well in advance that in Chiapas region, where the M8.2 earthquake occurred, the probability for the occurrence of an extreme event was the highest compared to other regions in Mexico. Furthermore, in this region, the investigation of the entropy change of seismicity under time reversal identified that almost 3 months before the occurrence of this major earthquake, an extreme event was likely to take place there.