Adaptive cruise control (ACC), as a driver assistant system for vehicles, not only relieves the burden of drivers, but also improves driving safety. This paper takes the intelligent pure electric city bus as the research platform, presenting a novel ACC control strategy that could comprehensively address issues of tracking capability, driving safety, energy saving, and driving comfort during vehicle following. A hierarchical control architecture is utilized in this paper. The lower controller is based on the nonlinear vehicle dynamics model and adjusts vehicle acceleration with consideration to the changes of bus mass and road slope by extended Kalman filter (EKF). The upper controller adapts Model Predictive Control (MPC) theory to solve the multi-objective optimal problem in ACC process. Cost functions are developed to balance the tracking distance, driving safety, energy consumption, and driving comfort. The simulations and Hardware-in-the-Loop (HIL) test are implemented; results show that the proposed control strategy ensured the driving safety and tracking ability of the bus, and reduced the vehicle’s maximum impact to 5 m/s3 and the State of Charge (SoC) consumption by 10%. Vehicle comfort and energy economy are improved obviously.