The development of methods increasing plant water use efficiency (WUE) would enhance the ability to grow wild aromatic and medicinally important species. The aim of this research was to determine the effect of plant growth regulators (PGRs) applied by spraying on stress resistance and WUE of fennel subjected to water stress. Plants in the generative stage were more drought tolerant than those in the vegetative stage. Water stress at vegetative stage decreased plant biomass and grain yield by 60% and 61%, respectively. Severe water stress in vegetative stage reduced grain production by 56%, and grains had 43% lower mass than those from non-stressed plants. Application of PGRs at both stages of growth increased grain yield and biomass, but the magnitude of increase depended on the type and application time of PGRs. Plants grown in well-watered conditions and sprayed with methyl jasmonate during the vegetative stage had the highest grain production (2.7 g plant−1), whereas under moderate water stress, plants yielded the best (2.1 g plant−1) when sprayed with epibrassinolide. The maximum WUE for grain (0.91 g L−1) and essential oil production (20 mg L−1) was noted in plants exposed to moderate stress and treated with methyl jasmonate during the vegetative stage