Boys Town was founded on December 12, 1917, as an orphanage for boys. Originally known as “The City of Little Men”, the organization was begun by Edward J. Flanagan, a Roman Catholic priest, while he worked in the Diocese of Omaha. Using a loan of $90, he first rented a home at 25th and Dodge streets, in Omaha, to care for five boys, the first of whom was named John Kresse From these beginnings, the City of Little Men developed new juvenile care methods in 20th-century America, emphasizing “social preparation as a model for public boys’ homes worldwide.” Eventually, their methods expanded to care for troubled teens and they expanded to include girls in their facilities.

The national headquarters of Boys Town is in the village of Boys Town, Nebraska, which was listed on the National Register of Historic Places, and was designated a National Historic Landmark, on February 4, 1985.

Facilities include the Hall of History, dedicated to the history of Boys Town; the restored home of Father Flanagan; the Dowd Memorial Chapel and the Chambers Protestant Chapel; and the Leon Myers Stamp Center. The latter provides historical stamp-collecting exhibits and sells donated stamps to provide support for Boys Town programs.

It has a summer camp on West Lake Okoboji, located near West Okoboji, Iowa.

In 1977, Boys Town founded and continues to operate the Boys Town National Research Hospital, located at 555 N. 30th Street in Omaha. Its sister hospital, Boys Town National Research Hospital – West, is operated on the Boys Town campus. The NPO also operates several medical clinics in Nebraska and one in Iowa.

Boys Town has grown over the years, providing care to children and families across the country. There are nine sites across the United States, in Central Florida, North Florida, South Florida, Louisiana, Nebraska, Iowa, New England, Nevada, and Washington, D.C.

In 2015, a former supervisor at a Boys Town group treatment home was convicted of having sex with a minor, aged 17. The offender, a 32-year-old woman, was sentenced to five years probation. On appeal, the conviction was affirmed by the Supreme Court of Nebraska.