The coronavirus disease 2019 (COVID-19) pandemic significantly impacted pharmacy students' education and well-being. The primary aim of this study was to evaluate the effects of the pandemic on students' perceived stress by comparing third- and fourth-year students from the pre-pandemic Class of 2019 with mid-pandemic Class of 2021 at two public institutions. Secondary aims were to evaluate the pandemic effects on students' academic and professional development skills and practice readiness. The Perceived Stress Scale (PSS) and the Brief Coping Orientation to Problems Experienced (COPE) scale were used to measure student well-being. Students' self-rated problem-solving, time management, and study skills were used to measure their academic and professional development; practice readiness was measured using students' self-rated confidence levels. PSS scores were significantly higher in mid-pandemic than pre-pandemic students, and the Brief COPE avoidant coping subscale differed between pre-pandemic and mid-pandemic students. No differences were found in any academic and professional development skills between the pre- and mid-pandemic students, and there were significant improvements in student confidence levels for practice readiness among the mid-pandemic students. In conclusion, the pandemic appeared to affect students' stress and avoidant coping mechanism but had variable effects on academic and professional development and practice readiness.