[7] Walker's manihot is native to the Lower Rio Grande Valley of Texas in the United States and Tamaulipas in Mexico.

Associated woody plants include Acacia rigidula, Citharexylum brachyanthum, Cylindropuntia leptocaulis, Karwinskia humboldtiana, Leucophyllum frutescens, and Prosopis glandulosa.

Walker's manihot has been collected from the Loreto caliche sand plain in Tamaulipas, where it grew alongside Asclepias prostrata, Manfreda longiflora, and Physaria thamnophila.

[7] Walker's manihott is a close relative of the widely cultivated cassava (M. esculenta) and has been studied for its role in introducing valuable traits into the latter.

This trait can be passed to M. esculenta × M. walkerae hybrids,[9] allowing the roots to remain intact one month after harvest.