Background: Antimicrobial resistance represents one of the most consequential public health emergencies of the twenty-first century, driven predominantly by the inappropriate and excessive consumption of systemic antibiotics in ambulatory healthcare settings. Acute respiratory tract infections constitute the single most frequent diagnostic indication for outpatient medical consultations worldwide and account for the vast majority of unnecessary antibiotic prescriptions despite their overwhelmingly viral and self-limiting etiology. Although numerous stewardship strategies have been trialed in general practice and family medicine, comparative synthesis of their clinical effectiveness, safety, and behavioural mechanisms remains essential for guiding health policy. Objective: This systematic review aimed to evaluate and qualitatively synthesize evidence from randomized controlled trials investigating the effectiveness and clinical safety of primary care interventions designed to reduce inappropriate overall or broad-spectrum antibiotic prescribing for patients presenting with acute respiratory infections. Methods: A comprehensive systematic literature search was conducted across MEDLINE via PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science to identify randomized controlled trials and cluster randomized controlled trials published in peer-reviewed journals. Eligible studies evaluated clinician-targeted, patient-targeted, diagnostic point-of-care, behavioral, or health-system interventions implemented in primary care practices for acute upper or lower respiratory tract infections compared with usual care or alternative stewardship strategies. Methodological quality was appraised using the revised Cochrane Risk of Bias tool for randomized trials. Due to substantial heterogeneity across intervention modalities and outcome metrics, a structured thematic qualitative data synthesis was performed in accordance with PRISMA 2020 guidelines. Results: From 2,480 initially identified records, 1,868 unique citations were screened after deduplication, 74 full-text articles were evaluated for eligibility, and nine landmark randomized controlled trials encompassing more than 440,000 patient consultations across Europe and North America were included in the final qualitative synthesis. Point-of-care C-reactive protein testing and enhanced clinician communication skills training demonstrated pronounced, synergistic reductions in antibiotic prescribing ranging from 31% to 62% relative risk reductions. Shared decision-making training programs and delayed antibiotic prescribing strategies reduced patient antibiotic consumption by 25% to 64% compared with immediate prescribing. Multifaceted educational outreach, peer academic detailing with personalized audit and feedback, and behavioral economics nudges such as accountable justification and peer comparison significantly reduced both overall inappropriate prescribing and broad-spectrum antimicrobial selection without increasing hospital admissions, suppurative bacterial complications, or unplanned reconsultations. Conclusion: Multifaceted primary care interventions that combine diagnostic uncertainty reduction, structured clinician-patient communication, delayed prescribing safety nets, and socially anchored audit and feedback safely and substantially reduce unnecessary antibiotic prescribing for acute respiratory infections.