Because velvetleaf is so difficult to control once established, prevention is important. Multiple control strategies may be needed to bring about control.

Velvetleaf seed is often scattered to new fields during harvest. Game animals and livestock can also transport seed. Individual plants can be removed by hand-pulling or hoeing, but plants should be burned because seed can mature even after the plant is pulled from the ground.

Crop rotation appears to reduce amount of velvetleaf seed in the soil because varying cultural practices ensures that the weed will not have continuously favorable conditions.

No biological control agents are currently available for velvetleaf. While it is a host for tobacco budworm (Heliothis virescens) and bollworm (H. zea), these insects are serious crop pests and cannot be encouraged for control of velvetleaf.

Herbicides can be effective against this weed, but velvetleaf has developed resistance to some widely used chemicals, including atrazine and Roundup® (glyphosate).