He has researched wolves since 1958 in locations including northern Minnesota, Isle Royale, Alaska, Yellowstone National Park, Ellesmere Island, and Italy.

The project to create the facility, which he started in 1985, was an outgrowth of his wolf research as well as his ambition to educate people about the nature of wolves, so that they may come to respect the creature through understanding.

[3][4] From 1958 to 1962, Mech was a graduate student at Purdue, studying the wolves of Isle Royale, on Lake Superior,[5][4] beginning in 1958.

[6] His first book was The Wolves of Isle Royale, published in 1966 by the Department of the Interior, having evolved from his doctoral thesis.

He witnessed wolf interactions within a family unit and watched them hunting muskoxen; this type of research had not been done before.

"[5] Mech and photographer Jim Brandenburg together produced several articles and a film for National Geographic.

The Denali work involved studying the interactions between wolves and caribou, moose, and Dall sheep.

[10] An avid mushroom hunter and fur trapper, Mech has continued to support fishing, hunting, and trapping, which has led to criticism from animal protectionists.

After more than 45 years of population recovery, in 2020, the US Fish and Wildlife Service removed the gray wolf from the list of endangered species.

According to his findings, about 50% of young wolves over 5–10 months old must be killed each year to bring a wolf population under control.

The International Wolf Center lists approximately 140 articles written by Mech, published from 1987 to the present, primarily in scientific journals.