Spalding University celebrates almost two centuries of academic tradition and service, extending back to 1814 when the Sisters of Charity of Nazareth established Nazareth Academy at Nazareth, near Bardstown, Kentucky. The earliest public examination ceremony was held in 1825 with Henry Clay presiding and presenting the awards. The charter enabling the institution to confer academic diplomas was granted by the legislature of the Commonwealth of Kentucky in 1829. The name of the University honors Catherine Spalding, the founder of the Sisters of Charity of Nazareth, who was responsible for securing the 1829 charter and is also regarded as the founder of social work in the Louisville area.

As was the case with many 19th century academies for young women, Nazareth Academy not only conducted the standard secondary school curriculum but college subjects, as well, and served as a training center for sisters who were to teach in other schools. Before the turn of the century, 84 new schools and academies had been established by the sisters in various parts of the country.

During the Civil War, faculty and staff members of the school served as nursing sisters for both the Union and Confederate armies. Abraham Lincoln issued a letter of protection so that the sisters at Nazareth would not be disturbed. The sisters served both sides with distinction but always for the purpose of better caring for those in pain, in need, and in fear. Six of the 39 sisters who served in the Civil War died during that conflict.

In 1920 Nazareth College was opened in Louisville, Kentucky, as the first four-year Catholic college for women in the Commonwealth. One year later, Nazareth Junior College was formally opened on the old Nazareth campus. The two institutions were merged in 1940 into Nazareth College with two campuses. The two separated in 1961 to form Nazareth College at Nazareth and Catherine Spalding College in Louisville, but merged again in 1969 to form Spalding College. In 1971 all instructional activity was consolidated on the Louisville campus.

In 1973 the College was incorporated as an independent, urban, coeducational institution in the Catholic tradition for students of all traditions. In 1984, in recognition of the wide range of programs offered, the institution was designated Spalding University. The 2005 Carnegie Classification identifies Spalding University as a Doctoral/Research University.

In addition to selected associate's and bachelor's degrees, Spalding University currently offers a variety of graduate-level programs leading to the master's degree or the doctoral degree.

Today, the University maintains its characteristically innovative stance on the cutting edge of educational service to the greater Louisville community and beyond. A new schedule for daytime undergraduate students was introduced in Fall 2003. The schedule consists of seven 6-week sessions per year, enabling students to earn a bachelor's degree with a highly flexible schedule.