The seed for the first home-away-from-home for families of seriously ill and injured children was planted when Kim Hill, the three-year-old daughter of Philadelphia Eagles tight end Fred Hill, was diagnosed with leukemia. Hill and his wife camped out on hospital chairs and benches, ate vending machine food, and did all they could to keep Kim from seeing their sadness, exhaustion, and frustration. The Hills saw other parents around them, some from great distances, doing the same thing. Hotels were incapable of providing the emotional support families needed and were expensive, especially for lengthy stays. There had to be a better way.

In response to the Hill Family's concern for families, the Eagles football team, Dr. Audrey Evans (head of the pediatric oncology unit at Children's Hospital of Philadelphia), and several McDonald's restaurant owner-operators planned a St. Patrick's Day shamrock shake promotion. All of the sales proceeds were used to establish the very first Ronald McDonald House, which opened in Philadelphia in 1974.

A second House soon followed in Chicago in April 1977, with the help of the Chicago Bears NFL team, Within two years, ten more Ronald McDonald Houses had opened. In the next ten years, more than one hundred additional Houses opened, including the Ronald McDonald House located in Indianapolis (at the time one of the largest constructed).