The amalgamation of Laurentia’s Archean provinces ca. 1830 Ma was followed by ~700 m.y. of accretionary orogenesis along its active southeastern margin, marked by subduction of oceanic lithosphere, formation of arcs and back-arcs, and episodic accretion. This prolonged period of active-margin tectonic processes, spanning the late Paleoproterozoic and Mesoproterozoic eras, resulted in major accretionary crustal growth and was terminated by closure of the Unimos Ocean (new name). Ocean closure was associated with rapid motion of Laurentia toward the equator and resulted in continental collision that led to profound reworking of much of the accreted Proterozoic crust during the ca. 1090–980 Ma Grenvillian orogeny. The Grenvillian orogeny resulted in formation of a large, hot, long-duration orogen with a substantial orogenic plateau that underwent extensional orogenic collapse before rejuvenation and formation of the Grenville Front tectonic zone. The Grenvillian orogeny also caused the termination and inversion of the Midcontinent Rift, which, had it continued, would likely have split Laurentia into distinct continental blocks. Voluminous mafic magmatic activity in the Midcontinent Rift ca. 1108–1090 Ma was contemporaneous with magmatism in the Southwestern Laurentia large igneous province. We discuss a potential link between prolonged subduction of oceanic lithosphere beneath southeast Laurentia in the Mesoproterozoic and the initiation of this voluminous mafic magmatism. In this hypothesis, subducted water in dense, hydrous Mg-silicates transported to the bottom of the upper mantle led to hydration and increased buoyancy, resulting in upwelling, decompression melting, and intraplate magmatism. Coeval collisional orogenesis in several continents, including Amazonia and Kalahari, ties the Grenvillian orogeny to the amalgamation of multiple Proterozoic continents in the supercontinent Rodinia. These orogenic events collectively constituted a major turning point in both Laurentian and global tectonics. The ensuing paleogeographic configuration, and that which followed during Rodinia’s extended breakup, set the stage for Earth system evolution through the Neoproterozoic Era.