One of the most debated volcanic areas along the eastern coast of Mexico is Los Tuxtlas Volcanic Complex located in the south of the Veracruz state. This volcanic province stands out as an isolated massif between the Trans-Mexican Volcanic Belt to the NW and the Chiapanecan Volcanic Belt to the SE. Los Tuxtlas complex is surrounded by two large alluvial plains formed by the Papaloapan and Coatzacoalcos rivers, and include the active volcano San Martín Tuxtla, the last eruption of which occurred in 1793. The ages, distribution, morphology and geochemistry of the volcanic vents and lavas, particularly the co-existence of the alkaline and subalkaline suites, offer an excellent opportunity to understand, in space and time, the tectono-magmatic history of Los Tuxtlas in comparison with other similar volcanic complexes in the eastern Trans-Mexican Volcanic Belt. Most of the volcanic centers of Los Tuxtlas show NW-SE alignments. This vent arrangement is associated with a left-lateral fault system known as the Veracruz fault, the northwestern expression of which are the submarine volcanoes that form the Anegada High. This fault might be a reactivation of the ancient Tamaulipas-Oaxaca fault related to the opening of the Gulf of Mexico. Based on geomorphological, geochemical, petrographical, and 40Ar/39Ar data, we propose three different stages of volcanic activity for Los Tuxtlas: The older Montepío-El Vigía (7–1.4 Ma), the intermediate Santa Marta (1–0.5 Ma), and the younger San Martín Tuxtla (50 ka to present). The main focus region of this paper is the stratovolcanoes of the Sierra de Santa Marta, formed by at least four major NW-SE aligned volcanic edifices, which from NW to SE are Encanto (950 m.a.s.l; identified and named in this work for the first time), Yohualtajapan (1450 m.a.s.l), Santa Marta (1685 m.a.s.l), and San Martín Pajapan (1250 m.a.s.l). The geological map, the 40Ar/39Ar dates, and the geochemistry data indicate a NW-SE migration of the volcanic activity of the four stratovolcanoes that have created the sierra de Santa Marta. Petrography and chemistry of rocks suggest that the subalkaline rocks of the three magmatic stages were fed by subduction activity of the Cocos Plate. The alkaline suite is likely associated with asthenosphere upwelling and slab edge melting, facilitated by a slab tear of the south Cocos plate evolved since the Early Miocene.