Irrigation plays an important role in the region's food and fibre production. While only covering about 1% of the total area of the Macquarie catchment, irrigated agriculture contributes up to 25% of total agricultural production from the region.

Prior to the construction of Burrendong Dam, there was some irrigation carried out by pastoralists in the Macquarie Valley to water fodder crops and pastures for stock feed. The completion of Burrendong Dam in 1967 allowed expansion of the irrigation industry in the mid and lower areas of the valley.  There was some further expansion in the 1990s as irrigators with groundwater entitlements in the Lower Macquarie Groundwater Sources were encouraged to develop and make use of this water supply.

Irrigation farms can now be found along the fertile riverine plains and slopes close to the Macquarie River, in the seven off-river irrigation schemes of Narromine, Trangie-Nevertire, Tenandra, Buddah Lake, Marthaguy, Nevertire and Greenhide, and in the area around Narromine comprising the Lower Macquarie Groundwater Sources.

Irrigation in the region is quite diverse although cotton is the predominant crop and is concentrated on the floodplains around Narromine, Trangie and Warren. Cotton is an annual crop and can only be grown when there is sufficient water availability. Given this, there can be large variances in the total area of cotton grown in the valley in each year. A range of summer and winter cereals, pulses and oilseeds may also be grown under irrigation in rotation with cotton.

Upstream of Narromine, irrigation entitlement is used to water lucerne, vegetables, pastures, cereals and oilseeds. There are also a number of citrus and other permanent horticulture and viticulture plantings located around Narromine and Dubbo that rely on high security river water or groundwater.