The land use and land cover (LULC) changes driven by the growing demands of mankind have a considerable effect on ecosystem services and functions. The study was carried out in the north-eastern highlands of Ethiopia to (1) analyze the effect of LULC changes between 1984 and 2021 and (2) assess the spatiotemporal variations in ecosystem service values (ESVs) and elasticity in response to LULC changes. Using Landsat imageries from 1984 to 2021, the spatiotemporal changes in LULC were evaluated with supervised image classification using maximum likelihood algorithm in ArcGIS software. Six LULC types were subsequently categorized, with overall accuracy and Kappa coefficients above 87% and 0.87, respectively. The ESVs were then estimated based on the Benefit Value Transfer (BVT) approach employing modified conservative value coefficients. The findings revealed a significant increase in cultivated land (9759.1ha) and built-up area (10174.41ha) during the stipulated periods and a drop in other land use types. The forest loss gradually decreased from 4.1% in the second period (1991-2001) to 0.58% in the third (2001-2021), compared to the first of the 1.1% conversion rates. Similarly, the proportion of grassland and water bodies steadily reduced over the stipulated periods, by 1.15% and 2.3% per annum, respectively. The overall loss of ESVs in the study landscape was estimated to be 54.4 million US$ (67.3%), drastically decreasing from 80.3 million US$ in 1984 to 26.4 million US$ in 2021, driven by the declining area coverage of water bodies, grassland, and forestland. Regardless of the loss, the ecosystem functions of hydrological regulation (37.2, 35.0, 6.1, and 5.1 US$ ha-1yr-1), water supply (14.5, 13.6, 2.4, and 2 US$ ha-1yr-1), and food production (9.8, 10.0, 9.1, and 9.9 US$ ha-1yr-1) contributed the most to the total ESV of each year while disturbance regulation and cultural values were the least throughout the study periods. The coefficient of sensitivity (CS) analysis revealed that our estimates were relatively robust. The findings further showed that human-dominated land-uses at the expense of natural ecosystems are the primary drivers of LULC transitions and the ensuing loss of ecosystem services in the region. Thus, this calls for intensive work on more effective land use policies that encourage an integrated management approach, with a focus on safeguarding the sustainability of natural ecosystems.