The late Eocene (39–35 Ma), a pronounced greenhouse interval, was characterized by a series of shoaling events of the carbonate compensation depth and widespread carbonate dissolution. However, the mechanisms causing these high-amplitude and rhythmically paced climate‑carbon cycle perturbations over this unusually prolonged period (>1 Myr) remain enigmatic, especially in climatically sensitive mid-to-high latitudes. Here, we present the first high-resolution sedimentary carbonate and discrete geochemical data from late Eocene successions (38.5–35.5 Ma) recovered at International Ocean Discovery Program Site U1514 (paleolatitude ∼53–54°S) in the Southern Ocean. Our results reveal a distinct carbonate-depleted sedimentary interval during the late Eocene warmth (37.5–36.5 Ma), reflecting intense carbonate dissolution in the Southern Ocean. This interval was marked by intensified hydrological cycling and continental erosion, accompanied by a reduction in silicate weathering intensity across southwestern Australia. Simultaneously, peaks in carbonate dissolution in the Southern Ocean coincided with warm phases associated with 405-kyr eccentricity maxima. Given the coherence with multi-ocean carbonate records, we propose that the 405-kyr eccentricity forcing exerted a first-order control over the rhythmic fluctuations of the global calcite compensation depth during the late Eocene. Meanwhile, the inefficiency or failure of the silicate weathering thermostat driven by clay mineral dynamics, superimposed on the orbital forcing, contributed to the extended ∼1 Myr complete carbonate dissolution. These results, corroborated by carbon cycle modeling simulations, highlight the fundamental role of orbital forcing and silicate weathering in regulating and stabilizing the Earth's climate and carbon cycle over tectonic timescales.