Water-use efficiency in grapevines is dependent on the aerial and below-ground environment of the plant. Specifically, transpiration efficiency, the ratio of net carbon fixation to water loss, may be influenced by soil moisture and the leaf-to-air vapour pressure deficit (VPD) in the soil-plant-atmosphere continuum. The interactive effect of these abiotic parameters, however, has not been suitably investigated in field-grown grapevines. Accordingly, gas exchange of an anisohydric variety, Semillon, was assessed across a number of vineyards in two warm grape growing regions of NSW to ascertain how soil moisture and VPD interact to affect transpiration efficiency at the leaf level. Leaf gas exchange measurements demonstrated that the rate of transpiration (E) was driven by VPD, particularly under high soil moisture. Both high VPD and low soil moisture decreased photosynthesis (A) and instantaneous leaf transpiration efficiency (A/E). Increased intrinsic leaf transpiration efficiency (A/g) in response to drying soil was limited to vines growing in a non-irrigated vineyard. In this site A/g was negatively related to vine water status. VPD did not have a substantial influence on A/g in any vineyard. While VPD is the main driver for A/E, soil moisture is an important determinant of A/g. Under high VPD, stomatal closure in Semillon leaves was not substantial enough to suitably curtail transpiration, and as a consequence A/E declined. These data indicate that in warm climates, irrigation scheduling of anisohydric varieties must take into account both VPD and soil moisture so that vine water status can be maintained.