Additionally, it was right next to the old main road leading from Castelseprio at Varese on the Monte Ceneri to Lukmanier Pass.
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The 1449 Battle of Castione ended when the Condottiere Giovanni della Noce burned the village down and forced the armies of Uri and its allies to flee into the Val Mesolcina.
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Arbedo-Castione is served by the Castione-Arbedo station, situated within the municipality.
From 1907, Castione-Arbedo station was the principal interchange point between the Gotthard railway and the Bellinzona–Mesocco railway (BM), a metre gauge railway linking Bellinzona and various communities in the Val Mesolcina as far as Mesocco.
The comune is further known to students of Late Antiquity as the place where the famous silver platter of Ardabur Aspar, consul in 434, was found (in the Fosso Castione, a creek near Marsiliana).