Although volcanogenic massive sulfide (VMS) deposits can form within a wide variety of rift-related tectonic environments, most are preserved within suprasubduction affinity crust related to ocean closure. In stark contrast to the VMS-rich Appalachian sector of the Grampian-Taconic orogeny, VMS mineralization is rare in the peri-Laurentian British and Irish Caledonides. Economic peri-Gondwanan affinity deposits are limited to Avoca and Parys Mountain. The Tyrone Igneous Complex of Northern Ireland represents a ca. 484–464 Ma peri-Laurentian affinity arc–ophiolite complex and a possible broad correlative of the Buchans-Robert’s Arm belt of Newfoundland, host to some of the most metal-rich VMS deposits globally. Stratigraphic horizons prospective for VMS mineralization in the Tyrone Igneous Complex are associated with rift-related magmatism, hydrothermal alteration, synvolcanic faults, and high-level subvolcanic intrusions (gabbro, diorite, and/or tonalite). Locally intense hydrothermal alteration is characterized by Na-depletion, elevated SiO2, MgO, Ba/Sr, Bi, Sb, chlorite–carbonate–pyrite alteration index (CCPI) and Hashimoto alteration index (AI) values. Rift-related mafic lavas typically occur in the hanging wall sequences to base and precious metal mineralization, closely associated with ironstones and/or argillaceous sedimentary rocks representing low temperature hydrothermal venting and volcanic quiescence. In the ca. 475 Ma pre-collisional, calc-alkaline lower Tyrone Volcanic Group rift-related magmatism is characterized by abundant non-arc type Fe-Ti-rich eMORB, island-arc tholeiite, and low-Zr tholeiitic rhyolite breccias. These petrochemical characteristics are typical of units associated with VMS mineralization in bimodal mafic, primitive post-Archean arc terranes. Following arc-accretion at ca. 470 Ma, late rifting in the ensialic upper Tyrone Volcanic Group is dominated by OIB-like, subalkaline to alkali basalt and A-type, high-Zr rhyolites. These units are petrochemically favorable for Kuroko-type VMS mineralization in bimodal-felsic evolved arc terranes. The scarcity of discovered peri-Laurentian VMS mineralization in the British and Irish Caledonides is due to a combination of minimal exploration, poor-preservation of upper ophiolite sequences, and limited rifting in the Lough Nafooey arc of western Ireland. The geological and geochemical characteristics of the Tyrone Volcanic Group of Northern Ireland and peri-Gondwanan affinity arc/backarc sequences of Ireland and northwest Wales represent the most prospective sequences in the British and Irish Caledonides for VMS mineralization.