Red Cloud is the county seat of Webster County, sitting along the Republican River in south-central Nebraska just a few miles north of the Kansas state line. The town site was opened to homesteaders in 1870 and platted in 1872 by Silas Garber, who went on to serve as Nebraska's third elected governor (1875–1879); Webster County organized that same year and voted Red Cloud its county seat, a distinction the town has held ever since. Red Cloud takes its name from Red Cloud, the celebrated Oglala Lakota war leader.

Red Cloud is best known today as the childhood home of Pulitzer Prize-winning novelist Willa Cather. Cather was actually born in 1873 in the Back Creek Valley near Winchester, Virginia — not in Nebraska — but her family relocated to Webster County in 1883, when she was nine, and by 1885 had settled into the house at 241 North Cedar Street now preserved as the Willa Cather Childhood Home, a National Historic Landmark. Red Cloud and the surrounding prairie became the model, in fictionalized form, for settings in six of Cather's novels, including O Pioneers!, The Song of the Lark, My Ántonia (whose title character was inspired by Cather's childhood friend Annie Sadilek Pavelka), and A Lost Lady, which drew on the life of town founder Silas Garber's second wife. The National Willa Cather Center, opened in 2017 in downtown Red Cloud, houses the restored 1885 Red Cloud Opera House along with an archive of more than 8,000 Cather-related documents and artifacts. The historic properties associated with Cather's life — including her childhood home, the Pavelka Farmstead, and the Farmers and Merchants Bank building — were transferred in October 2022 from a decades-long state partnership to full ownership by the nonprofit Willa Cather Foundation, which now operates guided tours of the sites. Red Cloud's downtown carries an unusually high concentration of National Register of Historic Places listings for a town its size, driven largely by this Cather legacy.

Beyond literature, Red Cloud has produced a notable roster of residents: U.S. Representative William A. McKeighan; Control Data Corporation founder William C. Norris, an early computer-industry pioneer; World War II "Flying Tiger" fighter ace Robert T. Smith; and Donald Stratton, a survivor of the USS Arizona at Pearl Harbor who was among the last three men to have served aboard the ship that day. At its peak, Red Cloud's Burlington Depot saw as many as eight passenger trains a day.

Red Cloud, the Webster County seat, was platted in 1872 by future Nebraska governor Silas Garber and is best known as the childhood home of novelist Willa Cather, whose family settled here in 1883. The town and surrounding countryside inspired settings in six of her novels; the National Willa Cather Center and several NRHP-listed Cather sites, now owned by the Willa Cather Foundation, draw visitors from across the country.