Velvetleaf is a major weed in cultivated fields, particularly in soybean, corn, and cotton. It is highly competitive with crop plants and can cause significant losses in yield as it uses water and soil nutrients. It is also a host for a number of crop diseases.

Velvetleaf may gain a chemical advantage over crop plants. Extracts of the leaves and seeds have been shown to inhibit germination and growth of alfalfa, corn, radish, soybean, and turnip seedlings.

Velvetleaf is difficult to control or eliminate because it can produce millions of seeds per acre and its seeds can remain viable for at least 50 years.

Despite its weedy nature, velvetleaf has some beneficial uses. In China and India, the seeds are eaten and many parts of the plant are used for medicinal purposes. Long fibers from the stem and branches can be made into twine, cloth, paper, and fishing nets.