The river is considered scenic along much of its route, having a broad and shallow course passing through several mountain ridges and steeply lined water gaps.

It formed an early 18th-century frontier region in Pennsylvania and was the site of French-allied Native American attacks against English colonial settlements during the French and Indian War.

[3] The river flows southeast through Huntingdon and continues to the small village of Ardenheim, where the Raystown Branch, the longest of the Juniata's tributaries, enters from the southwest.

It was reportedly 14.5 feet (4.4 m) tall and contained carvings recording the history of the local Juniata Tribe.

The valley was later inhabited by the Lenape until a treaty negotiated by William Penn opened the land to east of the Allegheny Ridge to white settlement.

Parts of the original locks from the canal, as well as remnants of a dam approximately 1 mile (2 km) south of Millerstown, are still visible today.

Attempts are underway by the state to reintroduce the once-prevalent American shad, which went into decline largely because of dams on the river.

The National Book Award and Pulitzer prize-winning poet Galway Kinnell wrote of the river in a section of The Book of Nightmares (1971), entitled "Dear Stranger, Extant in Memory by the Blue Juniata" ("The Blue Juniata" was a well-known 19th-century parlor song).