In order to deal with the increase in human-caused impacts, Saudi Arabia is exploring new groundwater sources. Significant agricultural development in Wadi Al Dawasir has resulted in an overuse of groundwater resources. Constant monitoring of the wadi's groundwater is necessary in order to make informed decisions about the future of the wadi's groundwater resources and the local economy. The rate of groundwater depletion in the Wadi Al Dawasir drainage basin in northern Saudi Arabia was calculated by combining data from the advanced Gravity Recovery and Climate Experiment (GRACE) mission with outputs from a land surface model. The analysis covered the period from April 2002 to December 2021. The results are as follows: (1) the average terrestrial water storage fluctuation (ΔTWS) was calculated at −0.48 ± 0.02 cm yr−1; (2) the average soil moisture storage change (ΔSMS) was calculated at + 0.0008 ± 0.0002 cm yr−1; (3) the average groundwater depletion rate was computed at −0.48 ± 0.02 cm yr−1; (4) the average yearly rainfall data for the Wadi Al Dawasir was 90.1 mm; (5) The surface relief is creating eastward streams that carry surface water downstream; (6) Significant agricultural expansions over the past few decades can be observed through Landsat change detection; (7) Higher sediment accumulation varying from 400 to more than 3000 m is observed in the east, near the Wadi's downstream, where the Wajid aquifer can be found. The integrated approach is a cost-effective and efficient tool for accurately evaluating the variability of groundwater resources over large regions.