Its range extends on the northeast through Texas and into southwestern Kansas and Oklahoma and northwestern Louisiana (the South Central states), and west to southern California.

[10][11] The seeds are disseminated by livestock that graze on the sweet pods, and the shrubs can invade grasslands, with cattlemen regarding mesquites as range weeds to be eradicated.

[13] Neltuma glandulosa shrubs and trees provide shelter and nest building material for wildlife, and produce seed pods in abundance containing beans that are a seasonal food for diverse birds and small mammal species.

In Namibia, although an invasive species, it has qualities that have made it useful for humans, including: growing extremely rapidly there, having very dense shade, abundantly producing seed pods, and a readily available firewood.

[14] The indigenous peoples of California and southwestern North America use parts of N. glandulosa as a medicinal plant, food source, building and tools material, and fuel.

[16][17] The Pueblo peoples of New Mexico in the southwest United States use the seeds to produce mesquite flour for making traditional horno bread.