Silicate weathering is a key process by which CO2 is removed from the atmosphere. It has been proposed that mountain uplift caused an increase in silicate weathering, and led to the long-term Cenozoic cooling trend, although this hypothesis remains controversial. Lithium isotopes are tracers of silicate weathering processes, and may allow this hypothesis to be tested. Recent studies have demonstrated that the Li isotope ratio in seawater increased during the period of Himalayan uplift (starting ca. 45 Ma), but the relationship between uplift and the Li isotope ratio of river waters has not been tested. Here we examine Li isotope ratios in rivers draining catchments with variable uplift rates from South Island, New Zealand. A negative trend between δ7Li and uplift shows that areas of rapid uplift have low δ7Li, whereas flatter floodplain areas have high δ7Li. Combined with U activity ratios, the data suggest that primary silicates are transported to floodplains, where δ7Li and (234U/238U) are driven to high values due to preferential uptake of 6Li by secondary minerals and long fluid-mineral contact times that enrich waters in 234U. In contrast, in mountainous areas, fresh primary mineral surfaces are continuously provided, driving δ7Li and (234U/238U) low. This trend is opposite to that expected if the increase in Cenozoic δ7Li in the oceans is driven directly by mountain uplift. These data suggest that the increase in seawater δ7Li reflects the formation of floodplains and the increased formation of secondary minerals, rather than weathering of mountain belts.