Abstract Background Many of the acute infections that are seen in primary care and sometimes managed with antibiotics are self-resolving and antibiotics may be unnecessary. Information about the natural history of these infections underpins antibiotic stewardship strategies such as delayed prescribing and shared decision making, yet whether it’s reported in guidelines is unknown. We examined, in clinical guidelines, the reporting of natural history information and relevant antibiotic stewardship strategies for acute infections commonly seen in primary care. Methods A systematic review of national and international guidelines (2010 onwards), available electronically, for managing acute infections (respiratory, urinary, or skin and soft tissue). We searched MEDLINE, CINAHL, EMBASE, TRIP, and GIN databases and websites of 22 guideline-publishing organisations. Results We identified 82 guidelines, covering 114 eligible infections. Natural history information was reported in 49 (59.8%) of the guidelines and 66 (57.9%) of the reported conditions, most commonly for respiratory tract infections. Quantitative information about the expected infection duration was provided for 63.5% (n = 42) of the infections. Delayed antibiotic prescribing strategy was recommended for 34.2% (n = 39) of them and shared decision making for 21% (n = 24). Conclusions Just over half of the guidelines for acute infections that are commonly managed in primary care and sometimes with antibiotics contained natural history information. As many of these infections spontaneously improve, this is a missed opportunity to disseminate this information to clinicians, promote antibiotic stewardship, and facilitate conversations with patients and informed decision making. Systematic review registration CRD42021247048