In arid regions of the world, the conversion of native vegetation to agriculture requires the construction of an irrigation infrastructure that can include networks of ditches, reservoirs, flood control modifications, and supplemental groundwater pumping. The infrastructure required for agricultural development has cumulative and indirect effects, which alter native plant communities, in parallel with the direct effects of land use conversion to irrigated crops. Our study quantified historical land cover change over a 150-year period for the Walker River Basin of Nevada and California by comparing direct and indirect impacts of irrigated agriculture at the scale of a 10,217 km2 watershed. We used General Land Office survey notes to reconstruct land cover at the time of settlement (1860–1910) and compared the settlement-era distribution of land cover to the current distribution. Direct conversion of natural vegetation to agricultural land uses accounted for 59 percent of total land cover change. Changes among nonagricultural vegetation included shifts from more mesic types to more xeric types and shifts from herbaceous wet meadow vegetation to woody phreatophytes, suggesting a progressive xerification. The area of meadow and wetland has experienced the most dramatic decline, with a loss of 95 percent of its former area. Our results also show Fremont cottonwood, a key riparian tree species in this region, is an order of magnitude more widely distributed within the watershed today than at the time of settlement. In contrast, areas that had riparian gallery forest at the time of settlement have seen a decline in the size and number of forest patches.