Forty-three new U-Pb zircon ages from metasedimentary and igneous rock units throughout the Cobequid Highlands of northern mainland Nova Scotia, Canada, provide new insights into the Neoproterozoic evolution of this long-enigmatic part of Avalonia in the northern Appalachian orogen. Contrasts in ages and rock types resulted in the identification of fault-bounded Neoproterozoic assemblages of units forming the Bass River, Jeffers, and Mount Ephraim blocks. In the Bass River block, quartzite, metawacke, and minor calc-silicate rocks and marble (Gamble Brook Formation) with a maximum depositional age of 945 ± 12 Ma are associated with subaqueous mafic volcanic rocks, siltstone, and ironstone (Folly River Formation) and intruded by 615–600 Ma calc-alkalic subduction-related dioritic to granitic rocks of the Bass River plutonic suite. The contrasting Jeffers block forms most of the Cobequid Highlands and consists mainly of intermediate to felsic volcanic, epiclastic, and minor plutonic rocks. The western and eastern areas of that block yielded ages mainly ca. 607–592 Ma for both volcanic and plutonic rocks, whereas the central area has ages of ca. 630–625 Ma from both volcanic and plutonic rocks and inheritance in overlying Devonian conglomerate. The Mount Ephraim block forms the eastern part of the highlands and includes possible ca. 800 Ma quartzofeldspathic, semipelitic and pelitic gneiss and schist of the Mount Thom Formation, ca. 752 Ma volcanic arc rocks of the Dalhousie Mountain Formation and related 752–730 Ma gabbroic/dioritic to granitic plutons of the Mount Ephraim plutonic suite and Six Mile Brook pluton, as well as ca. 631 Ma granitoid rocks of the Gunshot Brook pluton. The pre–750 Ma high-grade regional metamorphism and deformation and 752–730 Ma subduction-related magmatism recorded in the Mount Ephraim block were previously unrecognized in Avalonia. Evidence from zircon inheritance and Sm-Nd isotopic data in igneous units suggests linkages among these now-separate areas, and comparison with other parts of Avalonia in the northern Appalachian orogen suggests similarity to southeastern New England.