This study employed data from the 2015 Chilean sample of the Programme for International Student Assessment to examine the factors that influence science achievement and factors that may reduce the gender gap in science achievement. Our research was guided by Eccles’ Expectancy-Value Theory, which focused on motivational factors that influence gender differences in students’ achievement choices and performance. Our results indicate that socioeconomic status (SES), motivation, enjoyment of science, expected occupational status, school SES, and class size are related to higher science achievement. Also, anxiety was negatively associated with science achievement. Implications for Chilean policymakers and school administrators to improve Chilean girls’ science achievement are discussed.