The first chapter of Kappa Psi Pharmaceutical Fraternity was founded on May 30, 1879 at Russell Military Academy in New Haven, Connecticut, by F. Harvey Smith. Known, at the time, as the "Society of Kappa Psi," the fraternity existed as a secret organization which helped teammates come together after a strenuous football game against Cheshire Military Academy. After the two teams met again on November 30, 1879, a second chapter was established at Cheshire Military Academy. Unfortunately, these two chapters were eventually forced to disband in 1899. 

The idea of making this society into a national organization developed in the minds of several of its members. In the fall of 1885, alumni from the three chapters came together and established the Alpha Chapter. The Alpha Chapter was comprised of all alumni from the original three chapters that were interested in joining. F. Harvey Smith was made Grand Alpha, with Preston W. Eldridge, Jr., Lewis Bishop, and Lewis Oakley along side him as officers. The officers held meetings until 1899, and, during that time, they made plans to establish collegiate chapters in some of the schools that members were expected to attend. 

The first collegiate chapter was established in the fall of 1898 by William F. Clark at the University of Maryland, School of Medicine at Baltimore. This was designated as the Delta Chapter. Around the same time, Albert Kaehrle and his brother entered Columbus University, College of Pharmacy. They installed the Gamma Chapter there on November 20, 1898. Preston Eldridge, Jr. and William F. Clark installed the third collegiate chapter, Beta Chapter, at the University College of Medicine at Richmond, Virginia on March 31, 1900. 

The past 100 years have seen the Fraternity computerize its Central Office and continue to broaden its services. The Kappa Psi Foundation was created in 1992. The Fraternity continues to grow in size with over 80,000 initiates. Over 25 percent of these members were initiated in the last 25 years. This is a great force which represents every important segment of the profession and includes many of the most distinguished names in the annals of American pharmacy.