The Appalachian Mountains were formed through multiple phases of Paleozoic orogenesis associated with terrane accretion. The timing, tempo, and significance of each event in New England are obscured by overprinting, the limits of geochronologic tools, and differences between lithotectonic domains. We present new monazite and xenotime geochronology, ⁴⁰Ar/³⁹Ar thermochronology, and major- and trace-element thermobarometry from major tectonic domains in southern New England and across multiple structural levels. These data show contrasting pressure-temperature-time (P-T-t) paths across tectonic domains and highlight eastward metamorphic overprinting associated with younger tectonic events. Our data and geochemical proxies suggest two major periods of crustal thickening, ca. 455–440 Ma and 400–380 Ma, and a heterogeneous record of thinning/exhumation. Ordovician (Taconic) crustal thickening postdates the interpreted accretion of the Moretown terrane by ~20 m.y. and may have been related to shallow subduction after subduction polarity reversal. Subsequent cooling and exhumation (440–430 Ma) may have been related to the end of the Taconic orogeny and opening of the Connecticut Valley basin. (Neo)Acadian tectono-metamorphism is recognized in accreted terranes of New England and is absent in the Taconic block. Amphibolite- to (high-pressure) granulite-facies metamorphism, slow cooling, and protracted anatexis ca. 400–340 Ma support the existence of a long-lived orogenic plateau in southern New England. Exhumation, which began at 340–330 Ma, may have involved ductile (channel) flow. The boundary between continental Laurentia and accreted terranes has been reactivated at multiple times and is presently manifested as a 12–15 km Moho step. At the latitude of our samples, Alleghanian-age tectonism (ca. 310–285 Ma) was limited to retrograde metamorphism, and relatively minor loading and exhumation in the vicinity of the Pelham dome. Our results highlight the sensitivity of the integrative petrochronologic approach and the transition of the eastern margin of Laurentia from terrane accretion to the formation of a high-elevation plateau.