The land use/land cover (LULC) changes in Yarmouk River Basin (YRB) over a period of 22 years (1987–2009) have been analyzed, using remotely sensed data and geographic information system. Methods of LULC changes involved thematic change, image difference, and the normalized difference vegetation index (NDVI). Patch Analyst 5 for ArcGIS was used for the spatial analysis of landscape patches. The results revealed drastic changes in the LULC, with an overall change of more than 79%. Agricultural expansion has occurred at the expense of rangeland (16%) and forest (14%), whereas urban areas have taken over 2.65% of the agricultural areas, 2.11% of the forest, and 1.3% of the rangeland. The values of image difference were in agreement with the increase of urbanization and deforestation activities, besides the increased cultivation activities. The decrease in NDVI values indicates a degradation of vegetation cover. Class area (CA), mean patch size (MPS), and number of patches (NumP) for rangeland have decreased from 39,386 ha, 5.62 ha, and 7010 in 1987 to 17,729 ha, 4.62 ha, and 3838 in 2009, respectively. Similarly, CA, MPS, and NumP for forest land have decreased from 31,551 ha, 0.74 ha, and 42,548 in 1987 to 9558 ha, 0.65 ha, and 14,745 in 2009, respectively. Similar changes were shown to barelands. These results points to fragmentation of the natural land and habitat loss. On the other hand, CA and MPS of agriculture have increased from 35,306 ha and 0.72 ha in 1987 to 78,991 ha and 8 ha in 2009, respectively, indicating agricultural expansion. In addition, CA and NumP of urban have increased from 5513 ha and 89 in 1987 to 16,393 ha and 1536 ha in 2009. At the landscape level, the MPS has increased from ≈ 1 ha in 1987 to 3.7 ha in 2009, whereas NumP has decreased from 146,463 in 1987 to 38,006 in 2009, which means that the landscape became more clumped and continuous. The Shannon diversity index and Shannon evenness index have decreased, indicating that the landscape became more homogenous and more even over the 22 years of the study. It is believed that the major driver of LULC changes in the study area is urban growth, which usually leads to habitat disturbances.