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At the ecosystem scale, water-use efficiency (WUE) is defined broadly as the ratio of carbon assimilated to water evaporated by an ecosystem. WUE is an important aspect of carbon and water cycling and has been used to assess forest ecosystem responses to climate change and rising atmospheric CO2 concentrations. This study investigates the influence of meteorological and radiation variables on forest WUE by analyzing an 18 year (1998-2015) half-hourly time series of carbon and water fluxes measured with the eddy covariance technique in an old-growth conifer forest in the Pacific Northwest, USA. Three different metrics of WUE exhibit an overall increase over the period 1998-2007 mainly due to an increase in gross primary productivity (GPP) and a decrease in evapotranspiration (ET). However, the WUE metrics did not exhibit an increase across the period from 2008 to 2015 due to a greater reduction in GPP relative to ET. The strength of associations among particular meteorological variables and WUE varied with the scale of temporal aggregation used. In general, vapor pressure deficit and air temperature appear to control WUE at half-hourly and daily time scales, whereas atmospheric CO2 concentration was identified as the most important factor controlling monthly WUE. Carbon and water fluxes and the consequent WUE showed a weak correlation to the Standard Precipitation Index, while carbon fluxes were strongly dependent on the combined effect of multiple climate factors. The inferred patterns and controls on forest WUE highlighted have implications for improved understanding and prediction of possible adaptive adjustments of forest physiology in response to climate change and rising atmospheric CO2 concentrations.