Representation of diverse groups in science, technology, engineering, and mathematics (STEM) fields is a persistent concern in the United States. Although there have been some strides toward more diverse representation, significant problems of underrepresentation remain in particular STEM fields: physical sciences, engineering, math, and computer sciences (PEMC). The purpose of this study is to understand the significance of pre‐college personal and academic factors along with early college experiences to explain persistence among first‐generation college students (FGCS) considering possible differences among PEMC‐STEM majors, other‐STEM majors, and non‐STEM majors. Using institutional and survey data from one 4‐year urban research institution in the Southeast, logistic regression models demonstrate the importance of early academic performance (first‐semester GPA) to increase odds of FGCS persistence across majors; and also reveal important differences. Besides early academic performance, the only other significant factor for persistence of PEMC‐STEM majors was perceived preparation in math. Perceived social fit was significant for persistence for the other‐STEM and non‐STEM majors, whereas perceived academic fit was only significant for non‐STEM majors. These results align generally with previous research, and also suggest that examining differences among STEM subgroups may help develop more nuanced understandings of the needs of different groups. © 2015 Wiley Periodicals, Inc. J Res Sci Teach 53: 368–383, 2016