The One Pot method of methamphetamine production is a variation of older lithium-ammonia reduction methods that enable methamphetamine production in a single reaction vessel, which is commonly a plastic bottle. The lithium-ammonia reduction method of methamphetamine production, such as the One Pot method, uses lithium as an electron source to reduce the hydroxyl group on pseudoephedrine or ephedrine, forming methamphetamine. In order to determine whether One Pot methamphetamine laboratories can be detected through wastewater sampling, the current study collected 105 wastewater samples in Oklahoma (OK), South Carolina (SC), and Georgia (GA). They were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) for the presence of methamphetamine, pseudoephedrine, amphetamine, and the One Pot by-product, 1-(1,4-cyclohexadienyl)-2-methyllaminopropane (CMP). Grab and 24-hour composite samples were collected at gravity-fed manholes, lift stations, and two wastewater treatment plants (WWTPs) in multiple communities. Data from sewage water collection systems in SC, GA, and OK indicate levels of methamphetamine and pseudoephedrine in the range of nanograms per milliliter, which is not sufficient to identify cook waste. The data suggest that nanogram per milliliter levels of methamphetamine may occur routinely as a biological marker from methamphetamine users. The nanogram per milliliter presence of pseudoephedrine is likely to be from over-the-counter consumption. The highest levels of methamphetamine in this study correspond to low pseudoephedrine levels. This suggests that the high consumption was not sourced from a One Pot lab.