In the context of the increasingly intensified innovation competition, improving industrial innovation efficiency is the key to achieving the sustainable development of the old industrial base. This paper adopts the thinking of regional research to study the laws of industrial innovation in the old industrial base and takes the lock-in effect as the connection point between the industrial evolution history and industrial innovation efficiency. Based on the perspective of the lock-in effect, the three-stage industrial innovation model, the lock-in effect identification method, and the extended Porter model are creatively constructed. This paper chooses Jilin Province in Northeast China as a case, dissects the evolution history of industrial innovation in detail, and uses super-efficiency DEA, the Granger test, geographical detectors, and the panel regression method for quantitative analysis. The results show the following: (1) The lock-in effect faced by the industrial innovation of the old industrial base is significant, which has an impact on industrial innovation through industrial structure, enterprise composition, management system, and degree of marketization. (2) The lock-in effect causes the old industrial base to fall into an unhealthy circle in which it is difficult for industrial enterprises to obtain sufficient benefits through industrial innovation and the ability of industrial enterprises to absorb regional innovation resources is weakened. (3) The impact mechanism of industrial innovation in the old industrial base is very complex and the lock-in effect factors are not all negative. The improvement of industrial innovation in the old industrial base needs to increase the role of market forces, reform large traditional enterprises, and increase foreign economic ties. However, it also needs policy support, and it should avoid overly radical industrial transformation and enterprise strategies.