Calflora was started in 1994 by Ann Dennis while at the US Forest Service to help assess how management practices might affect wildlife, plant diversity, and forest health. Originally an 8-character DOS filename, Calflora was a database of species information that could be downloaded and used on a personal computer. Subsequent versions made the taxon table a web-searchable database, and tested the three table concept of taxon, synonymy and occurrence data. An important early collaborator was the Texas A&M University Bioinformatics Working Group.

In 1997, Calflora began collaborating with the UC Berkeley Digital Library Research Project to unite the Calflora database with a collection of wildflower images. Digital Library Project staff members including Ginger Ogle, Joyce Gross, Jeff Anderson-Lee, and Loretta Willis provided invaluable assistance in advising and developing the original CGI-based technical infrastructure of Calflora. The nucleus of the CalPhotos wildflower image collection was formed by a donation of scanned slides from photographer and amature botanist Brother Alfred Brousseau of St. Mary's College. This was upplemented by additional major photo donations from the California Academy of Sciences, California Department of Food and Agriculture, and many private individuals. Calflora has worked with CalPhotos to expand their collection of California native plant photos and weed photos.

Tony Morosco also joined Calflora in 1997 to begin assembling a library of observation data on California plants. In January of 2000 Ann Dennis, Tony Morosco, John Game, Emily Roberson, and Dean Taylor founded the public benefit corporation The Calflora Database to ensure the future of Calflora's services.

Calflora is an independent organization dedicated to providing scientific information about California plants for research, conservation, and education. Calflora is supported by a mixture of funding from government agencies, grants from foundations, and private donors. Many other individuals and organizations also contribute data, expertise, and technical support.

For more recent information, see Summary of 2009 or Working with CNPS Chapters.