High-level synthesis (HLS) enables designers to customize hardware designs without the need for delving into low-level hardware details. However, it is still challenging to establish the correlation between power consumption and hardware designs at an early design stage such as HLS. To overcome this problem, we introduce HL-Pow, a pre-register-transfer-level (pre-RTL) power modeling and optimization framework for FPGA HLS with the aid of up-to-date artificial intelligence techniques, which features high accuracy, speed and generalization ability. HL-Pow is comprised of a power modeling framework and a design space exploration (DSE) engine. The power modeling framework encompasses (1) a fully customized and light-weight feature construction flow to effectively identify and capture features that exert a major influence on power consumption; and (2) a modeling flow that can build an accurate, fast and transferable pre-RTL power estimator. With HL-Pow, the power evaluation process for hardware designs with FPGA HLS can be significantly expedited by circumventing the invocation of the time-consuming logic synthesis, physical design and gate-level simulation steps. Furthermore, we describe a novel a priori knowledge-guided DSE algorithm which can combined with our power modeling approach to jointly achieve the design optimization for latency and power consumption with high efficiency and high quality. Experimental results demonstrate that HL-Pow produces accurate power prediction that is only 4.82% away from onboard power measurement, while offering a speedup of 24–190× (84× on avg.). In addition, HL-Pow shows high generalization ability across applications with different characteristics and from various domains. Finally, the proposed DSE algorithm can reach a close approximation of the real Pareto frontier while only requiring traversing a small subset of design points in a broad design space.