The institute's annual funding comes from a combination of private donors, grant-making foundations, government science agencies, and companies affiliated with its business network.

The Santa Fe Institute was founded in 1984 by scientists George Cowan, David Pines, Stirling Colgate, Murray Gell-Mann, Nick Metropolis, Herb Anderson, Peter A. Carruthers, and Richard Slansky.

Originally called the "Rio Grande Institute", the scientists sought a forum to conduct theoretical research outside the traditional disciplinary boundaries of academic departments and government agency science budgets.

[5] As the idea of interdisciplinary science increased in popularity, a number of independent institutes and departments emerged whose focus emphasized similar goals.

Recent research has included studies of evolutionary computation, metabolic and ecological scaling laws, the fundamental properties of cities, the evolutionary diversification of viral strains, the interactions and conflicts of primate social groups, the history of languages, the structure and dynamics of species interactions including food webs, the dynamics of financial markets, and the emergence of hierarchy and cooperation in the human species, and biological and technological innovation.

The CSSS hosts 50–60 graduate students and early postdocs, along with select Business Network fellows, for a four-week course on complex systems.

Attendance at these lectures is free of charge, and in recent years many of the talks are recorded and made available on video platforms such as YouTube[26] The Santa Fe Institute has also launched a series of massive open online courses on complex systems, the first of which began in early 2013.

[27] In October 2019, The Santa Fe Institute launched Complexity Podcast, a general-audience weekly science discussion program featuring long-form interviews with SFI researchers.