Refractory rocks exposed in exhumed orogens have potential to preserve a record of high-pressure (HP) petrogenesis that is commonly obliterated in quartzofeldspathic rocks during high-temperature decompression. In the Montagne Noire migmatite dome (Variscan orogen foreland, France), eclogite is exposed in both the core (TdF, LJ) and margin (Cab) of the dome. We combine in situ U-Pb petrochronology (zircon, Zrn; rutile, Rt) and O-isotope analyses (garnet, Grt; Zrn) of key eclogite phases to investigate the protoliths, source regions, relative magnitude of deep crustal flow, and eclogite-migmatite fluid/melt interactions prior to exhumation. Dome-margin eclogite Zrn 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 Zrn with small relict cores and wide (15-30 µm) recrystallized rims. Protolith and HP metamorphism ages were determined using in situ Zrn and Rt petrochronology (LASS-ICP-MS). Dome-margin eclogite protolith Zrn cores formed in a continental setting at ~445 Ma; dome-core eclogite protolith Zrn grew at ~470 Ma. Both eclogites experienced HP metamorphism at ~315-310 Ma. Dome-margin Zrn cores and rims have the same 18O values within uncertainty (~8.3), in equilibrium with Grt (2 samples: ~8.0, ~8.2). In contrast, Zrn in two dome-core eclogites have statistically lower core 18O values (TdF: 9.70.1; LJ: 8.80.1) compared to their rims and neocrystallized grains (TdF:10.0-10.2; LJ: 9.2-9.3), with Zrn cores in 18O equilibrium with Grt (TdF: ~9.5, LJ: ~8.6). We propose that (1) gabbroic protoliths were emplaced in Cambro-Ordovician continental crust and subsequently experienced different fluid environments at HP in the Variscan; and (2) this multi-method, multi-systems approach to studying migmatite-hosted eclogite provides a way to qualitatively assess the magnitude and trajectory of deep orogenic crustal flow: the degree of Zrn recrystallization and Zrn geochemical signatures indicate that dome-core eclogites interacted extensively with surrounding migmatite during burial and foreland-vergent crustal flow, as opposed to the proximally-sourced dome-margin eclogite that experienced minimal interaction with surrounding migmatite during eclogite-facies recrystallization.