Identifying the relationships between ecosystem services (ESs) and land use change is crucial for ES management and sustainable regional development. The Manas region in China has witnessed dramatic reclamation activities in its desert areas that resulted in ecological problems. The changes in eight ESs, including crop production (CP), livestock production (LP), soil conservation (SC), water yield (WY), sand fixation (SF), carbon sequestration (CS), habitat quality (HQ), and nature landscape recreation (NLR), were investigated by using biophysical and questionnaire methods. At the regional scale, provisioning services (i.e., CP and LP) showed some performance improvements, whereas most of the regulating services (i.e., WY, CS, and HQ) along with NLR showed a performance decline. Five ES bundles—Upper Mountain, Foothill, Oasis, Oasis–Desert Transition, and Desert bundle—were identified at the township scale via k-means clustering. From 2000 to 2015, the Oasis bundle sprawled as a result of oasisization, whereas the Oasis–Desert Transition and Foothill bundles decreased. We performed a questionnaire survey and a statistical analysis to identify the causes behind the performance improvement/decline of these ESs and found that the land use changes in the Manas region had a significant impact on these services. More than 50% of the survey respondents identified land use changes as the primary driver of the changes in some ESs (i.e., CP, CS, HQ, and NLR). In the correlation and partial correlation analyses, oasisization was significantly and positively correlated with CP but was negatively correlated with WY, CS, HQ, and NLR. We enhanced the reliability of our conclusions by integrating biophysical and sociocultural methods into our investigation of ES and land use change. In view of the huge losses in regulating and cultural services, the Manas region should limit its desert reclamation activities to control the expansion of its oasis and to improve the quality of its cropland. Our results can help formulate effective ES management and land use decisions in the Manas region or similar areas.