Colossal magnetoresistance is a rare phenomenon in which the electronic resistivity of a material can be decreased by orders of magnitude upon application of a magnetic field. Such an effect could be the basis of the next generation of memory devices. Here we report CMR in the antiferromagnetic oxypnictide NdMnAsO1-xFx as a result of competition between an antiferromagnetic insulating phase and a paramagnetic semiconductor upon application of a magnetic field. Mn2+ oxypnictides are relatively unexplored, and tailored synthesis of novel compounds could result in an array of materials for further investigation and optimization.