Abstract Background The contamination of food by chemical hazards is a worldwide public health concern and is a leading cause of trade problems internationally. Based on former work describing the prevalent use and misuse of antibiotics in cattle in the Far North Region of Cameroon, we designed a study to detect antibiotic (penicillin G and oxytetracycline) in beef sold for human consumption in Maroua (Cameroon). To determine the mean concentration of antibiotic residues in beef, sample of liver and muscle were collected from 202 cattle selected randomly in all the slaughterhouses of Maroua and Godola and analyzed using Liquid Chromatographic tandem Mass Spectrometry (LC-MS/MS). Characteristics of the cattle selected (age, sex, breed, body condition score, weight, production system, and pathology, etc.) were also collected before and/or after slaughter – by physical examination and survey, and post mortem examination. Results Results revealed that out of 202 cattle 41 (20.30%) tested positive for antibiotics in one or more of their organs. The meat of cattle from transhumance system, sick animals and older cattle was more likely to be contained with penicillin G and oxytetracycline residues. The average residues concentration in beef was 17.58 μg/kg for penicillin G and 240 μg/kg for oxytetracycline. Conclusions The findings of the present study should be alarming for the legislative authorities in food security and safety. This highlights a very serious problem, both for the consumers of Maroua city and the herders of the region as well as for the whole economy of Cameroon. It is therefore be important that measures be taken at several levels by the actors of the sector (public authorities, veterinary auxiliaries, etc.) to guarantee the safety of the food of animal origin.