The Friends of Lakeside Lab would not exist without Iowa Lakeside Laboratory, one of the oldest and first biological field stations established in the United States, and the only such facility in the North American prairie pothole region. The Friends was organized in 1994 as a support organization for Lakeside and formally incorporated in 1996.

Founded in 1909 and today operated by the Iowa Board of Regents, Lakeside was the dream of Dr. Thomas Macbride, one of Iowa's first conservationists and leading scientists. Macbride was also a gifted educator who understood the importance of hands-on, field-based experiences to effective learning in the environmental sciences. Lakeside's mission to "teach about nature in nature", is a quote from Dr. Macbride.

With its location on the shores of Lake West Okoboji, its proximity to several state preserves, and a diversity of freshwater and terrestrial ecosystems - including Iowa's deepest, longest, and largest natural lakes - Lakeside is a choice location for teaching, research, and learning in the natural sciences.

After nearly a century of excellence in college and graduate-level teaching and research, however, Lakeside faced a crisis in the early 1990s when the Iowa Board of Regents recommended closing the Lab due to dropping enrollments and a dwindling state budget. In response, concerned citizens, Lakeside faculty, and alumni banded together to discuss how to save Lakeside. Under the leadership of the University of Okoboji Foundation, a task force formed and met with the Regents and university presidents, and convinced the Regents to reconsider their recommendation to close the Lab.

The individuals that rallied to save the Lab from closure did not retire their efforts but founded the Friends of Lakeside Lab to ensure continued support and community input into Lab operations.