Changes in teaching and learning practices were already taking place in higher education prior to COVID-19 as lecture attendance and student engagement was in decline. The rapid move to remote teaching and online classes forced further changes in the way we deliver classes, and changes to our teaching will continue as we determine the best practices to implement in the post-COVID future. Here, we use a large first-year biochemistry class as an example of the changes we have implemented to not only improve this course prior to and during the COVID pandemic, but also reduce student failure rates in a course that represents the challenges faced in the sciences, technology, engineering, and mathematics (STEM) disciplines. Before the pandemic, we supported student learning through quizzes with multiple attempts and introduced performance evaluations, reflections, and personal study plans, but during COVID we expanded on this, and introduced a biochemistry learning journal (ePortfolio). The digital learning journal contains integrated sections to create personal study plans and complete assignments in one digital learning platform. To supplement these assessment items, we developed weekly biochemistry activities to break the content into manageable chunks and aligned these with problem-based tutorials. From this experience, we will discuss those course improvements that will be maintained in detail, and provide an insight into future challenges and changes to further support student engagement, learning, and success.