This paper presents a novel method of seamline determination using region change rate (RCR) for orthoimage mosaicking. RCR is the change rate of the segmented region and is calculated based on the percentage of changed pixels in the segmented region. The presented method contains a two-level seamline optimization procedure to determine the final seamline using RCR. First, an object-level optimization based on image segmentation and change detection is executed to determine the allowed regions, i.e., the connected regions with minimized maximum RCR value through which seamlines are allowed to pass. This optimization is used to limit the maximum RCR along the seamline. Second, to determine the optimized seamline, pixel-level optimization is performed using Dijkstra’s algorithm based on differential cost. Finally, experimental results from digital aerial orthoimages and comparisons with other methods demonstrate the potential of the presented method for seamline determination.