The nearly nationwide range of honeylocust may be due to spread by Native Americans, who used the dried seeds and pulp as a food and sweetener.

Because honeylocust is hardy and fast growing, it is often used today as an ornamental or planted as erosion control. The thorns found on the trunk of the species are a major drawback for urban settings, but horticulture industry has developed thornless and fruitless varieties for landscaping.  

Because the dense, coarse-grained wood of the honeylocust is easily split and polishes nicely, it is commonly used a timber for fence posts, furniture, and pallets.