Background: Contamination of vegetables by multidrug resistant pathogens is of global concern. This is the first report on the antibiotic resistance of Escherichia coli and Salmonella enterica from lettuce and cabbage sources in the Tamale metropolis of Ghana. Method: A total of 26 Escherichia coli and 36 Salmonella enterica isolates were screened against nine antibiotics using the disc diffusion method. Results: The overall resistance (R), intermediate (I) and susceptibility (S) of Escherichia coli (n = 11) from the cabbages were 54.55%, 9.09% and 36.36%, respectively. Escherichia coli from cabbage samples were resistant to ofloxacin (100%), ampicillin (90.01%) and erythromycin (81.82%). The overall resistance, intermediate and susceptibility of Escherichia coli (n = 15) from lettuce samples were 52.59%, 10.37% and 37.04%, respectively. The isolates were also highly resistant to ofloxacin (100%), erythromycin (93.33%) and ampicillin (86.67%). The resistant patterns AmpOfxE, CroAmpTeOfxEC and AmpTeOfxEC (exhibited by 3 isolates each) were the commonest pattern among the Escherichia coli isolates. Overall resistance, intermediate and susceptibility of Salmonella enterica (n = 18) from cabbages were 48.77%, 11.11% and 40.12%, respectively. Salmonella enterica from cabbage samples were resistant to Ofloxacin (100%) and Erythromycin (94.4%). Overall resistance, intermediate and susceptibility of Salmonella enterica (n = 18) from lettuces were 53.70%, 10.49% and 53.70%, respectively. Lettuce Salmonella enterica isolates were also highly resistant to Ofloxacin (100%) and Erythromycin (94.4%). The resistant pattern AmpOfxE was the commonest among the Salmonella enterica isolates and was exhibited by 12 isolates. Multiple antibiotic index (MAR index) ranged from 0.33 to 0.67 for the Escherichia coli isolates. MAR index for Salmonella enterica also ranged from 0.22 to 0.78. Conclusion: This study revealed that cabbage and lettuce samples in the Tamale metropolis are contaminated with antibiotic resistant Escherichia coli and Salmonella enterica.