This study analyzed data from 1995, 2005, and 2015 using mathematical calculations, spatial analysis, and a geographically weighted regression model. The results showed that from 1995 to 2015, the comprehensive regional development degree (RDD) of urban agglomeration in the middle of Jilin Province increased overall, with the average RDD increasing from 0.250 in 1995 to 0.323 in 2015. Especially in Changchun, a sub-provincial city, the RDD increased by nearly one-third, and the gap between this and other cities has been increasing. However, the ecosystem service value (ESV) decreased overall, with the average ESV decreasing from 108.3 in 1995 to 105.4 in 2015, and showed a strong spatial correlation. The maximum quantile in southeast–northwest direction was 1.712, with good homogeneity. The spatial influence coefficient of the RDD on the ESV showed a trend from positive to negative in the northwest–southeast direction. This value decreased continuously while the negative agglomeration area was gradually expanding, corresponding to the stressful effects of the RDD on ESV. The results of this study can provide a reference for urban planning and development as well as encourage reasonable regional spatial planning to ensure the sustainable development of urban agglomerations.