Veterinary drugs are frequently employed to treat and prevent diseases in food-producing animals to improve animal health and to avoid the introduction of microorganisms into the food chain. The analysis of the presence of pharmaceutical residues in animal manure could help to evaluate the legal and illegal practices during food production without harming the animals and to correctly manage manure when it is going to be applied as a fertilizer. This article describes a method for the simultaneous analysis of 29 active substances, mostly antibiotics and antiparasitic agents. Substances were extracted from lyophilized manure with a methanol:McIlvaine solution and analyzed with HPLC–ESI-MS/MS and a C18 HPLC column. The method was validated following European guidelines, the achieved trueness was between 63 and 128% (depending on the analytes), and the linearity was between 100 and 1500 µg/kg. The applicability of the method was demonstrated in 40 manure samples collected from pig farms where tetracycline was quantified in 7.5% of the samples. These results show the viability of this non-invasive method for the control of the legal and illegal administration of pharmaceuticals in food-producing animals.