[5] Its natural habitat is in dry, often calcareous areas, including glades, bluffs, and open woodlands.

Euphorbia missurica grows in dry, sunny, sparsely vegetated habitats.

[8] It is found growing on rocky or sandy soils in dry prairies and waste places and roadsides.

[9] Its distribution includes the US states of: AR , CO , IA , KS , MN , MO , MT , ND , NE , NM , OK , SD , TX , WY.

[9] In Minnesota it is listed as a special concern species, where it has in the past been found in Ottertail County on sandy shorelines.