Area wide layout is an essential factor that significantly affects the safety, transportation and land occupation of chemical industrial zones. This research proposes a novel methodology to optimize the large-scale area-wide layout design for industrial zones. In layout design, the piping connection between processes is one of the essential issues. However, the complicated pipeline networks and pipe rack have not been taken into account before. Additionally, the current algorithm cannot solve the practical large-scale problem effectively. In this work, a new model and an optimization framework are proposed to solve the general layout problem. In the model, the piping layout and the pipe rack are designed in segments. The layout, pipe connections and pipe arrangement in the pipe rack are optimized simultaneously. Safety, geography and environmental constraints are considered in the optimization. A case study demonstrates the large-scale optimization can effectively reduce the total cost by 14.35% in less than 50 s. The impacts on the area-wide layout of the consideration of multi-utility and pipe rack are also analyzed. (C) 2020 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.