Second-term general chemistry is a key gateway course at our institution for a variety of STEM (Science, Technology, Engineering, and Mathematics) majors. Herein, we examine data on DFW% (i.e., % of D and F grades and withdrawals) in our general chemistry courses over roughly a quarter-century period, focusing on sections taught by the authors. The data are discussed in light of changes in curriculum, pedagogy, and assessments, which included introduction of recitation sections, classroom response systems (clickers), and online homework, restructuring of course content into a modular format, followed by a redesign of the course modules along an anchoring concepts scheme, introduction of the flipped classroom, and introduction of regular low-stakes quizzing. We find that the lowest DFW%, roughly 5%, occurs in classrooms combining an active learning pedagogy, core concepts curriculum, and low-stakes assessments with instructor intervention. Trends in the DFW populations are examined for White, non-Hispanic students, first-generation students, and by binary gender. We find that women are increasingly underrepresented in the DFW population, which may reflect the recent incorporation of lower stakes assessments. To the degree that our lowest DFW rates are consistent with that found by other researchers using different but related approaches, these may represent a baseline target for DFW rates in general chemistry II. Finally, while a trend toward lower DFW rates is found for both general chemistry I and II, the follow-on course, organic chemistry I, shows an inverse trend, which emphasizes the need for larger scale reform.