In the tallgrass prairies of western Missouri, gray dogwood tends to be restricted to the dry, rocky exposures within prairies and to edges along fencerows and wooded draws. In the loess hill prairies of northwest Missouri, this shrub can encroach on open prairies and, through competition and shading, reduce the area available for herbaceous prairie vegetation. Gray dogwood is a woody perennial that forms thickets from rhizomes. Sexual reproduction begins at about three to four years. One viable seed is produced in each fruit.
Hybridization occurs between gray dogwood and the similar species listed above.
A variety of bird species eat the fruits and disperse the seeds below perching sites. At least one report suggests that gray dogwood seeds have a low rate of germination. Dormancy may not be broken during the first winter following deposition. Its ability to effectively spread vegetatively may compensate for a lower reproduction by seeds. Groundcover vegetation diminishes beneath thickets of gray dogwood although annual weeds can persist.