Abstract Exploration and mining of lithium pegmatites has increased in recent years to meet the growing demand for critical metals, which are required for electric-powered transportation as well as sustainable energy production and storage. Pegmatite deposits produced approximately 60% of global lithium production in 2018, the vast majority of which was from spodumene pegmatites. However, there is lack of comprehensive models linking mineral system evolution and structural controls of lithium pegmatites. The majority of studies on lithium pegmatites have focused on chemical fractionation and assume that pegmatites have evolved from a parental granitic source, yet problems emerge when the connection between the granitic source and the pegmatite bodies is not obvious. This lack of connection has given rise to an alternative model of pegmatite formation, the anatectic model. In the anatectic model, granitic pegmatites form from granitic melts produced by partial melting of a suitable lithology, typically pelitic metasediments, without forming a large granitic body followed by fractional crystallization. Here, we first examine the formation of granitic melts related to anatexis, as well as how regional crustal structures influence chemical composition, crustal migration, and melt accumulation within the crust. We next examine the Wekusko Lake pegmatite field located in Manitoba, Canada, in terms of the probable melt source migration, the relationship between crustal-scale strain-zones and spatial pegmatite emplacement, and the chemical fractionation trend that records the formation of lithium-enriched pegmatites.