Environmental proteins (eProteins), such as Cry proteins associated with genetically engineered (GE) organisms, are present in ecosystems worldwide, but only rarely reach concentrations with detectable ecosystem-level impacts. Despite their ubiquity, the degradation and fate of Cry and other eProteins are mostly unknown. Here, we report the results of an experiment where we added Cry proteins leached from GE Bt maize to a suite of 19 recirculating experimental streams. We found that Cry exhibited a biphasic degradation with an initial phase of rapid and variable degradation within 1 h, followed by a slow and steady phase of degradation with traces of protein persisting after 48 h. The initial degradation was correlated with heterotrophic respiration and water column dissolved oxygen, confirming a previously documented association with stream metabolism. However, protein degradation persisted even with no biofilm and was faster at a more acidic pH, suggesting that water chemistry is also a critical factor in both degradation and subsequent detection. We suggest that Cry, as well as other eProteins, will have a rapid degradation caused by denaturation of proteins and pH changes, which confirms that the detection of Cry proteins in natural streams must be the result of steady and consistent leaching into the environment.