Characterizing the spatial transmission pattern is critical for better surveillance and control of human influenza. Here, we propose a mutation network framework that utilizes network theory to study the transmission of human influenza H3N2. On the basis of the mutation network, the transmission analysis captured the circulation pattern from a global simulation of human influenza H3N2. Furthermore, this method was applied to explore, in detail, the transmission patterns within Europe, the United States, and China, revealing the regional spread of human influenza H3N2. The mutation network framework proposed here could facilitate the understanding, surveillance, and control of other infectious diseases.