This study investigated the influence of practical problem-solving tasks (PPST) in promoting meaningful learning (ML) and retention in a nonlaboratory chemistry component of a physical science course for pre-service teachers (PSTs). It utilized a mixed-methods research using a modified quasi-experimental design followed by a detailed analysis of change in the conceptual understanding of case participants. The researcher employed mechanical and statistical matching to select 80 participants in two intact groups. The study’s findings revealed that using PPST as a mode of instruction significantly promoted ML and meaningful retention of chemistry concepts. The study generated patterns of explanation, patterns of change in the level of conceptual understanding, and patterns of regression in understanding. The study further argued that PSTs exposed to PPST experienced ML as evidenced by (1) the outcome–significant differences in performances in ML and meaningful retention tests, (2) the process–qualitative evidence of positive change in conceptual understanding, and (3) the context–use of PPST designed for PSTs to engage in a learning process meaningfully. This study called for further research on the inclusion of PPST in other nonlaboratory classes in chemistry and other science subjects, both at secondary and tertiary level.