We defined the seismotectonic setting of the external Marche Apennines (central Italy) by integrating geomorphological, structural and seismological data. The area is characterized by strong historical earthquakes, but the geometries and kinematics of the seismogenic sources have not previously been well defined. Plio-Quaternary Apennine compressional NW–SE structures are segmented by NE–SW-oriented transversal faults, the origin and role of which are still debated. We characterized the geometry, kinematics and activity of the four main transversal faults to better define their seismogenic potential. These high-angle, deeply rooted transversal fault systems have been mapped and separate the external Apennine sector into blocks and sub-blocks with different structural and evolutionary features. The integrated dataset showed that some inherited fault segments have recently been reactivated, displacing Quaternary deposits. The spatial distribution of seismicity indicates that some clusters of hypocentres are located within the basement. Stress field analysis using available focal mechanism solutions confirms the prevalence of left-lateral kinematics on roughly SW–NE-oriented structures. The transversal structures thus contribute to the longitudinal segmentation of the Apennine structures and, more generally, are involved in the northern part of the Adria plate kinematics towards the north and NNW. The assessment of seismic hazards and planning to mitigate risks in populated areas close to the Adriatic coast should consider these potentially active faults evidenced by instrumental seismicity and important historical earthquakes.