It is widely distributed in western North America, inhabiting conifer and mixed broadleaf forests, woodlands, grasslands, and chaparral biomes.

[3] Like other members of the genus Toxicodendron, T. diversilobum causes itching and allergic rashes in most people after contact by touch or smoke inhalation.

[2] The plant is winter deciduous, so that after cold weather sets in, the stems are leafless and bear only the occasional cluster of mature fruit.

[6] Botanist John Howell observed that the plant's toxicity obscures its aesthetic values: Toxicodendron diversilobum is found in California (Los Angeles was built on the site of a village named Yaangna or iyáanga’, meaning "poison oak place"),[8] the Baja California Peninsula, Nevada, Oregon, Washington, and British Columbia.

[4] The plant often occurs in chaparral and woodlands, coastal sage scrub, grasslands, and oak woodlands; and Douglas-fir (Pseudotsuga menzesii), hemlock–Sitka spruce, Sequoia sempervirens (coast redwood), Pinus ponderosa (Ponderosa pine), and mixed evergreen forests.

The active components of urushiol have been determined to be unsaturated congeners of 3-heptadecylcatechol with up to three double bonds in an unbranched C17 side chain.

[18] In the dormant deciduous seasons the plant can be difficult to recognize, however contact with leafless branches and twigs also causes allergic reactions.

Urushiol is also found in the skin of mangos, posing a danger to people sensitized to T. diversilobum when eating the fruit while it is still in the rind.

[19][20] Californian Native Americans used the plant's stems and shoots to make baskets, the sap to cure ringworm, and as a poultice of fresh leaves applied to rattlesnake bites.

[21] Chumash peoples used T. diversilobum sap to remove warts, corns, and calluses; to cauterize sores; and to stop bleeding.