Conventional parallel six-axis acceleration sensing mechanisms have compact structures and wide operating bandwidths. However, their performance is fixed and cannot meet the measurement requirements under varying operating conditions. To address this problem, a variable-topology parallel six-axis acceleration sensing mechanism is proposed, and the influence of topology variation on sensitivity performance is investigated. First, the inertial mass block is designed as a metamorphic structure, which endows the sensing mechanism with variable-topology characteristics. Second, a two-dimensional visualization method is proposed to describe the branch-chain layouts of different topological configurations. Then, an analytical model of acceleration sensitivity is established. Finally, the sensitivity characteristics under different topological configurations and excitation conditions are analyzed, and sensitivity maps are obtained. The results show that topology reconfiguration can precisely regulate the sensitivity performance of the proposed sensing mechanism.