This article contributes to analyze spatial structure of the innovation performance in Huaihe Economic Belt. We select 11 indexes to construct the evaluation index system for urban innovation performance and make cluster analysis over the innovation performance indexes of the 21 cities in Huaihe Economic Belt. As a result, the 21 cities are divided into four clusters as follows: highest innovation performance, high innovation performance, low innovation performance and the lowest innovation performance. This article analyzes the spatial structure characteristics of the 4 clusters, and draws some conclusions: from the east to the west, the spatial structure shows the rough trend of gradient decrease; the area of high innovation performance in the lower reaches of Huaihe River shows a zonal distribution; the cities with low innovation performance are generally distributed in the middle and upper reaches of Huaihe River.