In exhumed orogens, refractory mafic rocks have the potential to preserve a record of petrogenesis and high-pressure (H P ) metamorphism that is commonly obliterated in quartzofeldspathic rocks owing to re-equilibration at high-temperature, low-pressure (L P –H T ) conditions. In the Montagne Noire (France) migmatite dome, located in the foreland of the Variscan orogen, eclogite is exposed in both the core and margin of the dome. In this study, we combine in situ U Pb petrochronology and oxygen-isotope analyses of key eclogite phases to demonstrate that eclogites from the two distinct domains had different protoliths and source regions, traveled relatively variable distances in the deep crust, and differentially interacted with surrounding migmatite prior to exhumation. Dome-margin eclogite zircons are small (~40 μm) with well-preserved inherited cores and thin (<15 μm) rims, compared to larger (40–120 μm) neo- and recrystallized dome-core zircons with small relict cores and wide (15–30 μm) recrystallized rims. Protolith and H P metamorphism ages were determined using in situ zircon and rutile petrochronology (LASS-ICP-MS). Both eclogites formed in a continental setting; dome margin protolith zircon cores formed at 442.5 ± 3.4 Ma (steep HREE slope, no Eu-anomaly) whereas zircon cores of the dome-core eclogites yielded scattered dates suggesting protolith crystallization between ~500–400 Ma (steep HREE slope, pronounced Eu-anomaly). Both eclogites experienced H P metamorphism at c. 320–310 Ma in garnet-stable, plagioclase-absent conditions. Most analyzed rutile yielded dates of 307–304 Ma associated with cooling. The record of H P fluid conditions was determined by O-isotope (SIMS) analyses of garnet and zircon. Dome-margin zircon cores and rims have δ 18 O of ~8.2–8.5 ‰, indistinguishable within uncertainty, in isotopic equilibrium with isotopically unzoned garnet (δ 18 O ~ 8.0–8.2 ‰). In contrast, zircons in dome-core eclogites have systematically lower zircon-core δ 18 O values compared to their rims and neocrystallized grains, and zircon cores were in equilibrium with major-cation zoned garnet with respect to oxygen. The two dome-core eclogite samples yielded zircon and garnet δ 18 O values of ~8.6–9.5 ‰ and ~ 9.7–10.5 ‰. Based on these results and existing H P fabric data for these eclogites, we propose that (1) gabbro protoliths for the two eclogites were emplaced at different depths in a Cambro-Ordovician continental crustal package; and (2) dome-core eclogites interacted extensively with surrounding gneiss during burial and foreland-vergent crustal flow, whereas the dome-margin eclogite was sourced proximally to the dome-emplacement location and had minimal chemical interaction with surrounding gneiss. At least parts of the Montagne Noire migmatite dome were deeply sourced, but rocks exhumed in the core had a more extensive and protracted history of deep-crustal flow than deep-crustal rocks exhumed at the margin. • Eclogites in migmatite dome retain memory of deep crust history. • Zircon (re)crystallization extent reveals distinct eclogite source, flow paths. • Petrochronology and O-isotopes record migmatite-eclogite interaction at depth. • Integrated garnet, zircon datasets reveal protolith, peak, exhumation histories. • Domes may exhume crust laterally-sourced >100 s of km from emplacement location.