[1] The Kitkehahkis Pawnee villages farmed corn, beans, and pumpkin in the fertile Republican valley floor but seasonally left to hunt buffalo in the plains to the west and south.

[12] The Kansas Pacific Railway reached the fork of the Republican in 1866, crossing into the Junction City town site.

The Junction City and Fort Kearney Railroad was constructed up the valley of the Republican to Clay Center in 1873.

A public boat access ramp was opened on the mouth of the Republican River in 2009 just upstream of the railroad bridge,[17] providing access to the upper end of the Kansas River National Water Trail, a part of the National Water Trail program.

Allocation of the water from the Republican River is governed through an agreement called the Republican River Compact, involving the states of Nebraska, Kansas and Colorado, as modified by the settlement[19] of a United States Supreme Court case (Kansas vs. Nebraska and Colorado) involving a water-use dispute under the Compact.

[21] The storm of May 31 and June 1, 1935, (called "Nebraska's Deadliest Flood") dumped an average rainfall of 9 inches (230 mm) on the river's watershed.

As a result, the Frenchman, Red Willow, Medicine, Deer, Muddy, and Turkey creeks all reached their flood peaks at the same time as the crest passed on the Republican River.

According to witness accounts, the roar of the water could be heard coming down the Republican Valley 5 miles (8 km) away.

[22] Another account states that the Republican rose 10 feet (3 m) in 12 minutes in McCook, destroying the structures in its path.