Drawing on the coupling theory in physics, the coupling and coordinative mechanism of higher education agglomeration and regional innovation was analyzed, an evaluation index system of the two was established. Using the coupling coordination model to measure the coupling coordination degrees of the 11 cities in Zhejiang Province from 2005 to 2019, the spatial-temporal evolution process was analyzed by using spatial statistical tools. The results show that from 2005 to 2019, the comprehensive development index of higher education agglomeration in Zhejiang Province presented a fluctuating upward trend, and the comprehensive development index of regional innovation showed a spiral upward trend, higher education and regional innovation ability in Zhejiang Province has undergone an overall development, but there is an imbalance in the 11 cities. The coupling coordination degree of higher education agglomeration and regional innovation in Zhejiang Province is generally on the rise, the overall coupling coordination types was “near maladjustment and decline” in 2005, while the types became “grudging coordinated development” in 2019. The coupling coordination development level of higher education agglomeration and regional innovation in Zhejiang Province presented the spatial pattern of “coexistence of polarization-balance” and “obvious gradient differentiation of center-periphery”, the single-polarization pattern with Hangzhou as the pole transferred to the multi-center pattern with Hangzhou, Ningbo, Jiaxing as the centers, presents a gradient difference between northeast Zhejiang and southwest Zhejiang. Based on this, some countermeasures and suggestions are put forward for the coordinated development of higher education agglomeration and regional innovation in Zhejiang Province.