The idea for a Center for Quantitative Life Sciences emerged from discussions among the Mathematics and Biology faculty at Harvey Mudd.

In 2000, Michael Moody, then the chair of the Math Department, wrote a proposal to the Keck Foundation seeking funding to establish a Center. The proposal was funded in early 2001, and Lisette de Pillis and Steve Adolph became co-directors of the Center.

The Center was formally approved by the College in late 2002. The first Center visitors came in 2002, and the first sponsored research projects began in 2003.