The park is part of Minnesota's Pine Moraines and Outwash Plains Ecological Subsection and is contained within Clearwater, Hubbard, and Becker counties.

Approximately 7–8,000 years ago, Native American hunters pursued wild animals for food in the Itasca State Park region.

[3] The bison kill site along Wilderness Drive in the park gives visitors historical insight about this period.

In 1832 Anishinaabe guide Ozawindib led explorer Henry Schoolcraft to the source of the Mississippi River at Lake Itasca.

It was on this journey that Schoolcraft, with the help of an educated missionary companion, created the name Itasca from the Latin words for "truth" and "head" (veritas caput).

[4] In the late 19th century, Jacob V. Brower, historian, anthropologist and land surveyor, came to the park region to settle the dispute of the actual location of the Mississippi's headwaters.

Established in 1909, Itasca Biological Station and Labs (IBSL) is one of the oldest and largest continuously operated inland field training centers in the United States.

Each year new College of Biological Sciences students attend the "Nature of Life" orientation program which is held by the lake, allowing the study of a diverse, undisturbed environment from the organismal level to that of an entire ecosystem.

[6] Lake Itasca, the official source of the Mississippi River and a scenic area of northern Minnesota, has remained relatively unchanged from its natural state.

The retreat of the ice around 10,000 years ago left behind 157 lakes of varying size that cover 3,000 acres (12 km2) of Itasca State Park.

The glaciers deposited a moraine, a combination of silt, clay, sand, and gravel that covers the landscape to a depth of around 680 feet (210 m).

Fire is necessary to the regeneration of white, red, and jack pines in the area because it opens the forest floor and canopy for new trees to grow.

[9] The park is home to fourteen plants placed on the state endangered species list; these consist of ram's–head lady's slipper (Cypripedium arietinum), olivaceous spike–rush (Eleocharis olivacea), bog adder's–mouth (Malaxis paludosa), slender naiad (Najas gracillma), and sheathed pondweed (Potamogeton vaginatus).

[2] Itasca is home to over 200 bird species encompassing: bald eagles, loons, grebes, cormorants, herons, ducks, owls, hummingbirds, woodpeckers, chickadees, nuthatches, kinglets, vireos, tanagers, finches, and warblers.

Residing among the many trails in the park are over 60 types of mammals including beaver, porcupine, black bear, and timber wolves.

[11] It received this designation in November 1965 from the United States Secretary of the Interior, giving it recognition as an outstanding example of the nation's natural history.

[12] The designation describes its significance: The area contains some of the finest remaining stands of virgin red pine, spruce-balsam fir, and maple-basswood-aspen forest, supporting 141 bird and 53 mammal species, including bald eagles.

[11]Itasca State Park lies in northern Minnesota; a location that can be affected by three major air masses.

[9] In the summer, the Pacific and tropical winds from the Gulf create warm to hot temperatures, with the highs during July averaging 78.4 °F (25.8 °C).

A 9.6-mile (15.4 km) section of the North Country National Scenic Trail passes through the park's southern tier and includes three backcountry campsites.

[17] This structure is located along the south shore of Lake Itasca and was built using peeled logs harvested from the surrounding forests.

Douglas Lodge has provided tourist facilities since 1911 and remains functional today after undergoing renovations in the years following its grand opening.

In 1903 a 24-year-old park commissioner named Mary Gibbs played a significant role in saving the tall pine forests and shoreline of the Mississippi River Headwaters by resisting efforts to log the area.

In honor of her efforts, the Mary Gibbs Visitor Center, which encloses a restaurant, gift shop, various displays and exhibits of the park's features, and an outdoor plaza now exists.

Survey work on archaeological remains place human activity in the Itasca area as early as 8,000 years ago.

An initial finding of the remains of human made artifacts prompted the University of Minnesota to conduct an extensive excavation of the area in 1964 and 1965.

The site consists of ten burial mounds, dating back approximately 800 years, along the northeastern shore of Lake Itasca.