The behavior of Ti-Nb-Ta is crucial to reveal the genesis of island arc magmatism. However, mobilization and fractionation of Ti-Nb-Ta in subduction zone settings remain poorly understood. The discovery of felsic veins rich in coarse-grained rutile within retrograde eclogite of the North Qaidam UHP metamorphic belt provides a unique and novel opportunity to study age variation during rutile formation and alteration, as well as Ti-Nb-Ta mobility and fractionation during fluid/melt-rock interaction. Rutile high-resolution elemental mapping, and U-Pb bulk grain (ID-TIMS), and in-situ U-Pb geochronology have been utilized to focus on the properties of rutile in both, felsic vein and retrograde eclogite host to gain insight into possible similarities and differences. Three groups of rutile were distinguished according to its host rock, trace elements signature, and genetical connection to ilmenite: eclogite-hosted rutile (Rt-1), felsic vein-hosted rutile not associated with ilmenite (Rt-2a), and associated with ilmenite (Rt-2b). Field evidence and rutile trace elements characteristics document the source of vein-hosted rutile to be mainly derived from the eclogite during fluid/melt-rock interaction. Principal Component Analysis reveals that Nb, Ta, Sn, and W are more enriched in Rt-2a compared to Rt-1; Rt-2b has higher Nb, U, and Hf than Rt-2a. High-resolution mapping across large rutile grains shows the enrichment of high field strength elements (HFSEs) in rutile near to ilmenite, which indicates a HFSEs back diffusion from the rutile–ilmenite boundary during the replacement of rutile by ilmenite. The Nb/Ta ratios of Rt-2a are lower than those of Rt-1, which result from different partition coefficients of Nb and Ta during fluid/melt-rock interaction. The diffusion-influenced rutile exhibits suprachondritic Nb/Ta ratios and demonstrates that diffusion of Nb in rutile is higher than that of Ta under identical P-T conditions. Rutiles Rt-1 and Rt-2a yield consistent 206Pb/238U ages of 426–423 Ma, which is similar to the 433 ± 3 Ma determined by ID-TIMS results of bulk rutile grains. This indicates that Ti-Nb-Ta must have been mobilized during the exhumation of deeply subducted continental crust. However, the diffusion-influenced rutile shows a large variation of ages compared to the rutile not associated with ilmenite, demonstrating that the back-diffusion may affect the U-Pb system in rutile. Therefore, when rutile is partially altered into ilmenite or titanite, its dating should be used with caution. Thus, this study demonstrates volume diffusion is a very important geological process to result in extreme HFSEs fractionation and age variation of rutile on the mineral scale. The rutile aggerates that occur in the felsic veins in 3–5 m distance to the adjacent retrograde eclogite suggest that Ti-Nb-Ta-rich melts/fluids were transported over a distance of at least several meters and that rutile does not represent a residual phase of the Na-Si-Al-, F- and CH4-bearing fluid/melt environment that formed during anatexis of the subducted continental crust. The formation of rutile-rich aggregates during the generation, transport, and crystallization of subducted continental crust-derived melts/fluids in the deep roots of orogenic belts may be a critical trigger for the depletion of HFSEs in arc magmatic rocks during the formation of the continental crust.