This paper uses the entropy-weighted TOPSIS method to comprehensively evaluate the municipal economic development of prefecture-level cities in the Shanxi-Shaanxi-Inner Mongolia-Gansu-Ningxia (SSIGN) region. Then, it explores the spatio-temporal differentiation of economic development of the region using Markov transition probability analysis method and ESDA spatial analysis method. The results show that: (1) From 2005 to 2015, the gap in municipal economic development between cities in the SSIGN region was narrowed in the fluctuations, indicating that the municipal economic of the study region had not developed towards polarization, and there was a certain foundation for achieving coordinated development. (2) Each economic development grade city presented a diametrically opposite evolution law in different periods. Over time, all besides the lowest-grade cities had a higher risk of grade decline. This result indicates that for cities with higher municipal economic level, effective measures shoud be taken to improve their economic development sustainability. (3) From 2005 to 2010, to a certain degree, there was a significant spatial negative correlation between the economic levels of the cities in the SSIGN region. A positive interaction needs to be formed in this region. By 2015, this relationship was no longer significant. This result indicates that the municipal economic development of the region has improved in the direction of positive integration, but we still need to be alert to the problems of excessive homogenization and lack of effective interaction that have occurred in the historical development of this region. (4) The regional economic development of the SSIGN region has gradually emerged in the spatial pattern of the Golden Triangle consisting of Xi'an, Hohhot and Taiyuan. However, there has also been a clear cold spot in the study region. (5) The municipal economic development system in the cities of this region is generally in a state of low coupling coordination, and unbalanced economic development and uncoordinated are prominent. This result actually points out the key issue affecting the overall coordinated development of the region's economy. That is, the economic development subsystems within the city should also be a balanced system and coordinated development should be achieved among these subsystems.