Pegmatites enriched in the rare-earth elements ranging in age from Mesoproterozoic through Neoproterozoic occur along a southwestern trend from Wisconsin through Colorado to Arizona. Four widely geographically spaced pegmatite districts that are temporally associated with two distinct post-orogenic tectonic events are compared and contrasted in this study. The pegmatite districts include the circa 1.5 Ga Wausau syenite complex (WSC), in Wisconsin, the 1.0 Ga South Platte (SP), in Colorado, circa 1.6 Ga Trout Creek Pass (TCP), also in Colorado, and circa 1.5 Ga Mojave (MOJ) district in northwestern Arizona. The extreme enrichment of HREE in minerals such as polycrase-(Y), euxenite-(Y), samarskite-(Y) and xenotime-(Y), the LREE enrichment in monazite-(Ce), allanite-(Ce) and bastnäsite-(Ce), the REE enrichment in fluorite (where present), enrichments in high field-strength elements (HFSE) illustrated in chondrite-normalized plots and spider diagrams, as well as the intraplate signatures demonstrated in Pearce discrimination diagrams, indicate an anorogenic character for all the granite–syenite–pegmatite systems. All of the pegmatite districts are REE- and Nb-enriched, but TCP and MOJ are less strongly enriched than SP and WSC. The SP and WSC have the typical anorogenic NYF chemical signature, but TCP and MOJ are strongly depleted in F. These pegmatite-forming melts are all inferred to be crustally derived, with differences resulting from variable source-rock composition, differing degrees of partial melting, and perhaps the extent of rifting. The older TCP pegmatite district and the MOJ pegmatite district formed from melts derived by partial melting of lower crustal rocks with a significant metasedimentary component and are associated with smaller, localized extensional events subsequent to the Mazatzal orogeny, possibly related to back-arc spreading. The SP and WSC pegmatites are related to melts formed by the anatexis of lower crust during larger-scale rifting events. The greater enrichment in incompatible elements of WSC and SP pegmatites suggests that they originated from melts derived from smaller degrees of partial melting than pegmatites of TCP and MOJ, which are less strongly enriched and require larger degrees of partial melting. The F-depletion observed in TCP and MOJ pegmatites suggests a paucity of F-bearing minerals in the source region. More subtle geochemical differences between individual pegmatites appear to relate to the degree of evolution, which differs both within and across the pegmatite districts.