The Glacier Bay region of southeast Alaska, USA, and British Columbia, Canada, has undergone major glacier retreat since the Little Ice Age (LIA). We used airborne laser altimetry elevation data acquired between 1995 and 2011 to estimate the mass loss of the Glacier Bay region over four time periods (1995–2000, 2000–05, 2005–09, 2009–11). For each glacier, we extrapolated from center-line profiles to the entire glacier to estimate glacier-wide mass balance, and then averaged these results over the entire region using three difference methods (normalized elevation, area-weighted method and simple average). We found that there was large interannual variability of the mass loss since 1995 compared with the long-term (post-LIA) average. For the full period (1995–2011) the average mass loss was 3.93 ± 0.89 Gt a−1 (0.6 ± 0.1 m w.e. a−1), compared with 17.8 Gt a−1 for the post-LIA (1770–1948) rate. Our mass loss rate is consistent with GRACE gravity signal changes for the 2003–10 period. Our results also show that there is a lower bias due to center-line profiling than was previously found by a digital elevation model difference method.