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One critical component in the STEM educational pipeline is students’ interest and persistence in STEM majors—a function of students’ perceived value and expectancy beliefs. Through an expectancy-value lens, we examined cross-domain patterns of high school students’ expectancy beliefs and values in both mathematics and science using a person-centered approach. Latent profile analysis revealed five profiles characterized as Low Math/Low Science, Moderate Math/Moderate Science, High Math/High Science, Low Math/High Science, and High Math/Low Science. Accounting for students’ sociodemographics and school context, we found that motivational profile membership predicted math and science achievement, college persistence, and STEM major intentions and decisions. There were gender and racial differences and contextual variation in profile memberships. Implications for theory and educational practice are discussed.