Minimizing frame bus utilization is a difficult issue for a controller area network with flexible data rate (CAN-FD) in automotive cyber-physical systems (ACPS) due to the heterogeneity between frames payload and periods. Recently, the cluster-based method was used to solve the problem of CAN-FD frame packing. However, this method does not consider both payload and period and ignores the impact of signal sequence. In this study, we propose a cluster-based CAN-FD frame packing framework by presenting two strategies, namely, a strategy that maximizes frame size (MAXFS) and a strategy that minimizes frame bus utilization (MINFBU). We first use MAXFS to pack the signal with the same period into a frame and maximize the frame size; then, MINFBU is used to pack the signal into any frame and minimize bus utilization. Experimental results show that the proposed framework can reduce bus utilization and deviation rate more effectively compared with the state-of-the-art counterparts.