There is a significant concern about the accumulation of hazardous chemicals in the environment. Pharmaceuticals and drugs of abuse (DOA) can reach high levels in waste water and industrial or hospital effluents, for example. Another group of chemicals of concern are organophosphate compounds. Although the stockpiling and manufacture of chemical warfare agents (CWA) has substantially decreased due to the Chemical Weapon’s Convention, nerve agents continue to be used by rogue states and other actors. In this study, two paper spray MS screening procedures were developed to detect these hazardous chemicals in soil without sample preparation. Central nervous system (CNS) depressants, opiates, stimulants, and tricyclic antidepressants were included in the pharmaceutical/DOA screening method. Chemical warfare simulants and hydrolysis products were analyzed using a separate screening method which utilized polarity switching to detect positive and negative ions associated with this class of molecules. For both methods, an aliquot of soil was weighed into a well pressed against the paper spray substrate. A dual extraction/spray solvent was then applied to the soil, extracting the analytes and facilitating electrospray ionization from the paper. A quadrupole-orbitrap mass spectrometer was utilized in MS/MS mode for detection. Limits of detection for the pharmaceuticals and DOA ranged between 0.3 and 40 ng/g for three different soil types. The CWA simulants had limits of detection of 50 ng/g while the hydrolysis products were detected between 1 and 5 ng/g. In order to improve quantitative performance, an offline salting out liquid-liquid (SALLE) extraction with internal standardization was also performed.