Djerrasi died of complications of cancer in his San Francisco home, Stanford University spokesman Dan Stober said.
He was 91.
Djerassi, a professor emeritus of chemistry at Stanford, was most famous for leading a research team in Mexico City that in 1951 developed norethindrone, a synthetic molecule that became a key component of the first birth control pill.
"The pill," as it came to be known, radically transformed sexual practices and women's lives.
In his book, "This Man's Pill," Djerassi said the invention also changed his life, making him more interested in how science affects society.
"The thoughts behind these two public policy articles had convinced me that politics, rather than science, would play the dominant role in shaping the future of human birth control," he wrote.
He is survived by a son, Dale Djerassi; a stepdaughter, Leah Middlebrook; and a grandson, Alexander M Djerassi.