Weathering of uplifted continental rocks consumes carbon dioxide and transports cations to the oceans, thereby playing a critical role in controlling both seawater chemistry and climate. However, there are few archives of seawater chemical change that reveal shifts in global tectonic forces connecting Earth ocean-climate processes. We present a 68-million-year record of lithium isotopes in seawater (δ(7)Li(SW)) reconstructed from planktonic foraminifera. From the Paleocene (60 million years ago) to the present, δ(7)Li(SW) rose by 9 per mil (‰), requiring large changes in continental weathering and seafloor reverse weathering that are consistent with increased tectonic uplift, more rapid continental denudation, increasingly incongruent continental weathering (lower chemical weathering intensity), and more rapid CO(2) drawdown. A 5‰ drop in δ(7)Li(SW) across the Cretaceous-Paleogene boundary cannot be produced by an impactor or by Deccan trap volcanism, suggesting large-scale continental denudation.