The mass changes of the Gulf of Alaska (GoA) glaciers are computed from the Gravity Recovery and Climate Experiment (GRACE) inter-satellite range-rate data for the period April 2003–September 2007. Through the application of unique processing techniques and a surface mass concentration (mascon) parameterization, the mass variations in the GoA glacier regions have been estimated at high temporal (10 day) and spatial (2 × 2 arc-degrees) resolution. The mascon solutions are directly estimated from a reduction of the GRACE K-band inter-satellite range-rate data and, unlike previous GRACE solutions for the GoA glaciers, do not exhibit contamination by leakage from mass change occurring outside the region of interest. The mascon solutions reveal considerable temporal and spatial variation within the GoA glacier region, with the largest negative mass balances observed in the St Elias Mountains including the Yakutat and Glacier Bay regions. The most rapid losses occurred during the 2004 melt season due to record temperatures in Alaska during that year. The total mass balance of the GoA glacier region was −84 ± 5 Gt a−1 contributing 0.23 ± 0.01 mm a−1 to global sea-level rise from April 2003 through March 2007. Highlighting the large seasonal and interannual variability of the GoA glaciers, the rate determined over the period April 2003–March 2006 is −102 ± 5 Gt a−1, which includes the anomalously high temperatures of 2004 and does not include the large 2007 winter balance-year snowfall. The mascon solutions agree well with regional patterns of glacier mass loss determined from aircraft altimetry and in situ measurements.