The natural distribution of Vitis rupestris is concentrated in the Ozark Hills of Missouri and Arkansas.

There are a few reports of the species occurring in the San Francisco Bay area of California, but these are most likely escapes from cultivation.

[2][3][4] Vitis rupestris is a self-supporting bushy plant that does not grow in the shade, and is found only on rocky riverbanks and streambanks.

Vitis rupestris has been listed as threatened or endangered by Indiana, Kentucky, Pennsylvania, and Tennessee.

[5] Known locations of wild Vitis rupestris are quickly disappearing, which may threaten the future of this grape species.

[4] Wood is smooth and red when young, becoming cylindrical and finely striated when mature with dark colored bark that becomes darker with age.

'Vitis rupestris' often contributes a large proportion of ancestries of 'French hybrid' grapes (or 'French direct producers') such as Seyval, although it was often overlooked in its homeland in favor of Vitis labrusca.

A large proportion of modern European "PIWI" varieties categorized as Vitis vinifera contain 'Vitis rupestris' background such as Solaris and Regent.