Order picking is the most labour-intensive and costly activity for almost every warehouse. This paper has two main objectives: first, to propose two new routing heuristics for order-picking in a rectangular warehouse, Ascending and Ascending+, and second, to investigate the impact of order region on the performance of routing heuristics. Four experiments based on dividing the warehouse into 12 main regions and large numbers of randomly generated test problems are designed to validate the proposed heuristics' performance. The computational results demonstrate the effectiveness and efficiency of the ascending+ heuristic compared to the performance of the previously published heuristics. The statistical analysis reveals the significant impact of the order region on the performance of the routing heuristics. Therefore, each order region is allocated to the best-performed heuristic.