This mixed-methods study was designed to examine the perceptions of students from a rural area regarding Science, Technology, Engineering, Mathematics (STEM), and STEM careers. STEM perceptions of high school students from a rural setting were determined using the STEM Semantics Survey. Survey results were analyzed to determine the mean ratings for each of five scales (Science, Technology, Engineering, Mathematics, and Careers in STEM) and to determine similarities and differences in female and male STEM perceptions. Results of a MANOVA indicated that males had statistically significantly more favorable perceptions of STEM and STEM careers overall. Independent samples t-test results for each scale indicated that the significant difference in female and male STEM perceptions was driven by the large difference on the Engineering scale. Females perceived engineering significantly less positively than did males, though females did have a slightly more positive perception of the field of Mathematics than did males. College students who attended the same rural high school as the high school student participants also completed the STEM Semantics Survey. Results of the survey were used to develop interview questions for the college students. Interview data from the college students revealed strong beliefs that, because they attended a rural high school, they had fewer, less engaging, and less rigorous STEM experiences than college students they knew who had attended more urban high schools. This rural effect permeated all discussions of their STEM perceptions. Having few STEM role models in their community, limited STEM resources in their school and community, and a community that did not place a high value on STEM were mentioned by college students as influencing their perceptions of STEM and STEM careers.