We present an overview of the Eocene-Oligocene transition from a marine perspective and posit that growth of a continent-scale Antarctic ice sheet (25 × 10⁶ km³) was a primary cause of a dramatic reorganization of ocean circulation and chemistry. The Eocene-Oligocene transition (EOT) was the culmination of long-term (10⁷ yr drawdown and related cooling that triggered a 0.5‰–0.9‰ transient pre-scale) CO₂ cursor benthic foraminiferal δ¹⁸O increase at 33.80 Ma (EOT-1), a 0.8‰ δ¹⁸O increase at 33.63 Ma (EOT-2), and a 1.0‰ δ¹⁸O increase at 33.55 Ma (oxygen isotope event Oi-1). We show that a small (~25 m) sea-level lowering was associated with the precursor EOT-1 increase, suggesting that the δ¹⁸O increase primarily reflected 1–2 °C of cooling. Global sea level dropped by 80 ± 25 m at Oi-1 time, implying that the deep-sea foraminiferal δ¹⁸O increase was due to the growth of a continent-sized Antarctic ice sheet and 1–4 °C of cooling. The Antarctic ice sheet reached the coastline for the first time at ca. 33.6 Ma and became a driver of Antarctic circulation, which in turn affected global climate, causing increased latitudinal thermal gradients and a “spinning up” of the oceans that resulted in: (1) increased thermohaline circulation and erosional pulses of Northern Component Water and Antarctic Bottom Water; (2) increased deep-basin ventilation, which caused a decrease in oceanic residence time, a decrease in deep-ocean acidity, and a deepening of the calcite compensation depth (CCD); and (3) increased diatom diversity due to intensified upwelling.