Platinum-resistance is a major confounding factor in the clinical management of ovarian cancer resulting in close to 70% rate of relapse of treatment-resistant disease. In this study, we have used patient-derived cells from the Australian Ovarian Cancer Study to highlight the cellular and molecular dynamics of high grade serous ovarian cancer cells during the course of platinum treatment. Using an array of techniques, including live single cell tracking and single cell sequencing, combined with quantitative proteomics, we have demonstrated inherent cellular and molecular patterns of response to platinum, stratified along the resistance spectrum. Tracking of fluorescent-tagged ovarian cancer cells with the cell cycle reporter, FUCCI, clearly demonstrated distinct patterns of cell cycle plasticity among clonal lineages with varied levels of platinum response. Further, single cell sequencing during the course of treatment, has highlighted key signatures within defined clusters with heightened response to platinum, with the remainder clusters demonstrating a clear resistance to treatment. Quantitative proteomics of chromatin-bound protein fractions in single cell-derived clones with varied response to platinum, further highlighted discrete signatures of arrest with key elements of DNA repair machinery and nuclear skeletal remodeling. Altogether, our findings provide a comprehensive single-cell resolution overview of cellular and molecular dynamics in high grade ovarian cancer cells during the course of platinum response. An image that will further elucidate the mechanisms behind development of resistance, providing biomarkers for molecular prognostics and targets for novel treatments.