Drylands, particularly in the developing countries are highly affected by climate change. Major devastating changes are expected to happen in dryland areas, ecosystem structures, productivity and socio-economic characteristics of inhabitants. This study aimed at investigating drylands’ socio-economic and biophysical characteristics and assesses its vulnerability to changes in temperature and rainfall. The Northern Jordan Valley region, Palestine was selected as a pilot study area. Direct meetings and a questionnaire were used to collect socio-economic and agricultural data over the period February–July 2019. Soil samples were collected from representative fields in the study area to test the major soil chemical properties. A large climatic dataset (1970–2019) was analyzed to investigate changes in rainfall and temperature. Results show that the average households’ monthly income in the study area was in the range US $440–900. A significant portion of households’ monthly income was spent on water for domestic and agricultural purposes. Water harvesting was a predominant activity due to water scarcity in the study area. The chemical analysis of the soil samples revealed that the salinity in the irrigated area was more likely a result of the farmers’ agricultural practices. Analysis of climatic data of the Northern Jordan Valley revealed a reduction in annual rainfall by 4.5 mm/decade during the period 1970–2019. In addition, the average monthly values of maximum and minimum temperatures of the same period have exceeded the long-term monthly average of maximum and minimum temperatures in the study area. These changes in rainfall and temperature has exaggerated water scarcity in the study area and provided strong evidence on climate change in the region. The high vulnerability of Northern Jordan Valley region to climate change has strongly impacted the livelihoods’ of its inhabitants and forced many people to immigrate.