The Desert Andes contain >4500 ice masses, but only a handful are currently being monitored. We present the mass changes of the small mountain glacier Agua Negra (1 km2) and of the rest of glaciers in the Jáchal river basin. Remote-sensing data show Agua Negra glacier lost 23% of its area during 1959–2019. Glaciological measurements during 2014–2021 indicate an average annual mass balance of −0.52 m w.e. a−1, with mean winter and summer balances of 0.80 and −1.33 m w.e. a−1, respectively. The Equilibrium Line Altitude (ELA) is estimated to be 5100 ± 100 m a.s.l., which corresponds to an Accumulation Area Ratio (AAR) of 0.28 ± 0.21. Geodetic data from SRTM X and Pléiades show a doubling of the loss rate from −0.32 ± 0.03 m w.e. a−1 in 2000–2013, to −0.66 ± 0.06 m w.e. a−1 in 2013–2019. Comparatively, the ice losses for the entire Jáchal river basin (25 500 km2) derived from ASTER show less negative values, −0.11 ± 16 m w.e. a−1 for 2000–2012 and −0.23 ± 14 m w.e. a−1 for 2012–2018. The regional warming trend since 1979 and a recent decline in snow accumulation are probably driving the observed glacier mass balance.