Increasing rigor in secondary school classrooms for college and career readiness is a priority throughout the nation with the adoption of more challenging standards for student performance and is an important role for school leaders in creating conditions in schools to meet this challenge (Young, 2012). P-16 partnerships can assist by aligning the expectations for high school and college students as part of P-16 efforts to bridge the gap between high school and college (Bloom, 2011; Chamberlain & Plucker, 2008; Ek, Machado-Casas, Sanchez, & Alanis, 2010). Yet, leadership is needed for P-16 alignment efforts to be successful (Rochford, 2005). The identification of benefits and challenges in promoting college and career readiness alignment for math and science can be useful as school leaders throughout the nation lead similar reform efforts. The purpose of this mixed-methods case study was to identify key benefits and challenges of a P-16 initiative to strengthen secondary and postsecondary math and science alignment in predominantly low-income, rural schools by working in collaboration with university professors, high school, and pre-service teachers to meet College and Career Readiness Standards. Both benefits accrued from the partnership as well as challenges that participants identified for full implementation will be discussed in this article.