One of the most important subduction zones in the world is located in the Mexican Pacific Coast, where the Cocos plate inserts beneath the North American plate. One part of it is located in the Mexican Pacific Coast, where the Cocos plate inserts beneath the North American plate with different dip angles, showing important seismicity. Under the central Mexican area, such a dip angle becomes practically horizontal and such an area is known as flat slab. An earthquake of magnitude M7.1 occurred on September 19, 2017, the epicenter of which was located in this flat slab. It caused important human and material losses of urban communities including a large area of Mexico City. The seismicity recorded in the flat slab region is analyzed here in natural time since 1995 until the occurrence of this M7.1 earthquake in 2017 by studying the entropy change under time reversal and the variability β of the order parameter of seismicity as well as characterize the risk of an impending earthquake by applying the nowcasting method. The entropy change ΔS under time reversal is found to exhibit a minimum on June 21, 2017 that is almost one week after the observation of such a minimum in the Chiapas region where a magnitude M8.2 earthquake occurred on September 7, 2017 being Mexico’s largest quake in more than a century. A minimum of β was also observed during the period February to March 2017. Moreover, researchers show that, after the minimum of ΔS, the order parameter of seismicity starts diminishing, thus approaching gradually the critical value 0.070 around the end of August and the beginning of September 2017, which signals that a major earthquake is going to occur shortly in the flat slab.