Patagonia, in the Southern Andes, is one of the few locations where interactions between the oceanic and continental lithosphere can be studied due to subduction of an active spreading ridge beneath the continent. In order to characterize the noble gas composition of Patagonian subcontinental lithospheric mantle (SCLM), we present the first noble gas data alongside new lithophile (Sr–Nd–Pb) isotopic data for mantle xenoliths from Pali-Aike Volcanic Field and Gobernador Gregores, Southern Patagonia. Based on noble gas isotopic compositions, Pali-Aike mantle xenoliths represent intrinsic SCLM with higher (U+Th+K)/(3He, 22Ne, 36Ar) ratios than the mid-ocean ridge basalt (MORB) source. This reservoir shows slightly radiogenic helium (3He/4He = 6.84–6.90 RA), coupled with a strongly nucleogenic neon signature (mantle source 21Ne/22Ne = 0.085–0.094). The 40Ar/36Ar ratios vary from a near-atmospheric ratio of 510 up to 17700, with mantle source 40Ar/36Ar between 31100−6800+9400 and 54000−9600+14200. In addition, the 3He/22Ne ratios for the local SCLM endmember, at 12.03±0.15 to 13.66±0.37, are higher than depleted MORBs, at 3He/22Ne = 8.31–9.75. Although asthenospheric mantle upwelling through the Patagonian slab window would result in a MORB-like metasomatism after collision of the South Chile Ridge with the Chile trench ca. 14 Ma, this mantle reservoir could have remained unhomogenized after rapid passage and northward migration of the Chile Triple Junction. The mantle endmember xenon isotopic ratios of Pali-Aike mantle xenoliths, which is first defined for any SCLM-derived samples, show values indistinguishable from the MORB source (129Xe/132Xe=1.0833−0.0053+0.0216 and 136Xe/132Xe=0.3761−0.0034+0.0246).The noble gas component observed in Gobernador Gregores mantle xenoliths is characterized by isotopic compositions in the MORB range in terms of helium (3He/4He = 7.17–7.37 RA), but with slightly nucleogenic neon (mantle source 21Ne/22Ne = 0.065–0.079). We suggest that this MORB-like metasomatism was capable of overprinting the noble gas composition of Gobernador Gregores due to recent metasomatism of the SCLM because of asthenospheric mantle upwelling in response to opening of the Patagonian slab window. The 40Ar/36Ar ratios vary from a near-atmospheric ratio of 380 up to 6560, with mantle source 40Ar/36Ar between 8100−700+1400 and 17700−3100+4400. The lower 40Ar/36Ar ratio of the Gobernador Gregores mantle source, compared with that of Pali-Aike, attests that the Patagonia SCLM was affected significantly by atmospheric contamination associated with the recycled oceanic lithosphere.