Wastewater treatment plants receive sewage containing high concentrations of bacteria and antibiotics. We assessed bacterial counts and their antibiotic resistance patterns in water from (a) influents and effluents of the Legon sewage treatment plant (STP) in Accra, Ghana and (b) upstream, outfall, and downstream in the recipient Onyasia stream. We conducted a cross-sectional study of quality-controlled water testing (January–June 2018). In STP effluents, mean bacterial counts (colony-forming units/100 mL) had reduced E. coli (99.9% reduction; 102,266,667 to 710), A. hydrophila (98.8%; 376,333 to 9603), and P. aeruginosa (99.5%; 5,666,667 to 1550). Antibiotic resistance was significantly reduced for tetracycline, ciprofloxacin, cefuroxime, and ceftazidime and increased for gentamicin, amoxicillin/clavulanate, and imipenem. The highest levels were for amoxicillin/clavulanate (50–97%) and aztreonam (33%). Bacterial counts increased by 98.8% downstream compared to the sewage outfall and were predominated by E. coli, implying intense fecal contamination from other sources. There was a progressive increase in antibiotic resistance from upstream, to outfall, to downstream. The highest resistance was for amoxicillin/clavulanate (80–83%), cefuroxime (47–73%), aztreonam (53%), and ciprofloxacin (40%). The STP is efficient in reducing bacterial counts and thus reducing environmental contamination. The recipient stream is contaminated with antibiotic-resistant bacteria listed as critically important for human use, which needs addressing.