The objectives of this work were to study prevalence and characteristics of resistance to antibiotics of staphylococcal isolates from the bulk-tank milk of sheep flocks across Greece, to assess possible associations of the presence of antibiotic resistance with the quality of milk in these flocks and to evaluate flock-related factors potentially associated with antibiotic resistance among these isolates. A cross-sectional study was performed in 325 sheep flocks in Greece. Bulk-tank milk samples were collected for bacteriological examination; staphylococcal isolates were evaluated for resistance to 20 antibiotics. Oxacillin-resistant staphylococcal isolates, isolates resistant to any antibiotic, and multi-resistant isolates were recovered from 8.0%, 30.5%, and 12.0% of flocks, respectively. Of 232 isolates, 11.6% were resistant to oxacillin, 46.1% were resistant to at least one antibiotic, and 16.4% were multi-resistant. Resistance was seen more frequently among coagulase-negative (50.6%) than among Staphylococcus aureus (31.5%) isolates. Resistance was more frequent against penicillin and ampicillin (34.1% of isolates), clindamycin (17.7%), and fosfomycin (14.2%). An association was found between biofilm formation by staphylococci and resistance to fosfomycin. For recovery of oxacillin-resistant isolates, the lack of experience by farmers emerged as a significant factor; respective factors for the isolation of staphylococci resistant to any antibiotic or multi-resistant isolates were the early stage of the lactation period (0th–1st month) and the intensive management system applied in the flocks, respectively.