<p>This study resolves the spatial and seasonal variations in prokaryotic abundance (PA) and biomass concerning physicochemical parameters during Spring Inter-Monsoon (April–May), Summer Monsoon (June–September), and Winter Monsoon (November–February) in the Eastern Arabian Sea. PA and biomass distribution estimated using microscopic techniques revealed their peak abundance during Spring Inter-Monsoon, ranging from 2.29–4.41 × 10⁶ Cells mL⁻¹ to 8.39–21.82 μgL⁻¹, respectively. Similarly, high PA and biomass were observed in late Summer Monsoon (September), ranging from 2.01–3.96 × 10⁶ Cells mL⁻¹ to 8.74–16.70 μgL^–1, respectively, which was preceded by a higher phytoplankton abundance (chlorophyll <i>a</i>- 14.57 mgm⁻³) during the peak Summer Monsoon (August). The Winter Monsoon, started with a low PA and phytoplankton abundance. As Winter Monsoon progressed, convective mixing promoted phytoplankton growth in the latter half until March. The decay released dissolved organic carbon (DOC), leading to a rise in PA from January to February, peaking during Spring Inter-Monsoon (first peak). With the advent of Summer Monsoon, upwelling enriched surface layers with nutrients to promote phytoplankton growth in August. The subsequent decaying phase generated higher DOC which enhanced PA by the end of Summer Monsoon (second peak). However, PA declined to its lowest levels by November. Distance-based linear model analysis indicated that temperature and chlorophyll <i>a</i> were the most influential factors affecting PA in the upper photic-zone, while ammonia, dissolved oxygen, and DOC were associated factors. In contrast, nutrients were the major determining factors in disphotic waters (200–2000&#xa0;m). This study highlights the intricate interplay between physicochemical and biological variables in shaping prokaryotic populations during various physical forcings through intense sampling efforts in the Arabian Sea.</p> Graphical Abstract <p></p>