Tri-Beta was founded in 1922 at Oklahoma City University by Dr. Frank G. Brooks and a group of his students. The idea of an honor and professional society for biology students spread rapidly and by 1925, the society was a national organization. Biennial national conventions of student and faculty members began in that year and in 1930 the society journal BIOS, began publication of student research, articles of interest to biologists, and society news. As the society grew, it was divided into regional and district groups, each of which holds a convention annually. At the heart of every district and national meeting are student research papers presented in the style of graduate meetings. Awards are given for outstanding individual and chapter accomplishments.

Individual membership in Tri-Beta is through a chapter on the campus of a four-year accredited college or university. There are now more than 370 chapters offering their members activities and experiences that enrich and extend but do not duplicate the primary requirements for the biology major. The national constitution provides a framework for chapter activities, but each chapter is free to function in accordance with its own needs and school philosophy. A national officer visits each prospective chapter as part of the application process. Chapter programs typically include guest speakers, reports of research by members and department faculty, field trips, maintenance of collections, community service, and social gatherings. Most chapters have a lounge or office on campus, and at least one chapter has maintained an entire house for its members. A faculty advisor provides continuity and experience to the student members.