Beatrice is located approximately 42 miles south of Lincoln on the Big Blue River.

While it was stranded, 35 of the passengers agreed to form the "Nebraska Association", under which name they would unite in seeking a townsite and establishing a settlement in the territory.

[6][7] After reaching Nebraska City, the Association divided itself into two exploratory parties, one of which went directly westward and the other southwest.

The latter party located the site of Beatrice, at the point where the DeRoin Trail crossed the Big Blue River, and the whole Association decided to settle there.

[10] In 1862, the U.S. Congress passed the Homestead Act, which allowed settlers to claim 160 acres (65 ha) of government land for a nominal fee.

Just after midnight on that day, Daniel Freeman persuaded a clerk to open the local Land Office so that he could file a claim for a homestead located 4 miles (6 km) west of Beatrice.

[11][12] In 1936, Congress created Homestead National Monument of America on the site of Freeman's claim.

[6][7] However, it represented a major obstacle to travelers on the Oregon Trail route;[5] and floods frequently destroyed the dams and bridges in the area.

[5][6] In 1871, the Burlington and Missouri River Railroad constructed a line from Lincoln, Nebraska to Beatrice.

[5] On August 3, 1892, future president William McKinley, then governor of Ohio, gave a campaign speech in Beatrice.

In 1885, the Nebraska legislature enacted legislation to establish the Institution for Feeble Minded Youth near Beatrice, subject to the city's donating a suitable parcel of land.

[8]: 303  Beatrice donated 40 acres, located 2 miles (3 km) east of the city limits, and the first residents were admitted in 1887.

The institution was largely self-supporting, operating a farm on which the residents did much of the work; in 1935, 346 acres (140 ha) were under cultivation.

[17] From there it declined: new restrictions had been imposed on the use of unpaid labor by residents of institutions, and there was a national trend toward deinstitutionalization.

[15] In 1975, the Horacek v. Exon lawsuit was settled with a consent decree whereunder many of the residents of the Beatrice State Home were transferred to community-based mental health facilities.

[18] In that year, the institution's name was changed to the current Beatrice State Developmental Center.

[33] A popular story was circulated about a near-miss that occurred in Beatrice, when, at 7:25 pm on March 1, 1950, a church was destroyed by a natural gas explosion five minutes after a scheduled choir practice was to start, but no one was injured because all fifteen members were late, and thus not present at the time of the explosion.

[35] A 1970 science fiction novel "The House in November" by Keith Laumer takes place largely in Beatrice, Nebraska.