San Francisco Girls’ School is a new all-girls independent high school with an outstanding STEM program. Its curriculum is built on extensive research showing that girls from single-sex high schools have superior academic achievement, greater participation in STEM, better social-emotional outcomes, stronger leadership skills and career results than their coed counterparts. Beyond the city, San Francisco Girls’ School has a broader mission of serving as an incubator for cutting-edge STEM coursework, designed specifically for girls, through its Center of Excellence for Girls’ STEM Education, and delivering it on-line for free to a national consortium of public girls’ schools. The Center of Excellence will combine data analysis from this pioneering public-private initiative with current research to refine best practices and develop a foundational pedagogy for teaching girls STEM. San Francisco Girls’ School aims to reverse the declining number of girls nationwide pursuing university STEM degrees and, later, STEM careers.