Background: This study aims to establish dominant factors influencing general practitioner (GP) decision-making on antibiotic prescribing in the Australian primary healthcare sector. Two research questions were posed: What influences antibiotic prescribing from the perspective of GPs? How do GPs trade-off on factors influencing antibiotic prescribing? Methods: An exploratory sequential mixed methods design was used, comprising semi-structured interviews followed by a discrete choice experiment (DCE). Ten GPs practising in Brisbane and Greater Brisbane, Queensland were interviewed in September/October 2015. Interview data were used to develop the DCE, which was conducted online from July–October 2016. Twenty-three GPs participated in the DCE. Results: Three main themes influencing antibiotic prescribing emerged from the semi-structured interviews: prescribing challenges, delayed antibiotic prescriptions, and patient expectations. From the DCE, “Duration of symptoms” and “Patient expectations” exerted the most influence on antibiotic prescribing. Taken together, these results suggest that key challenges to prudent antibiotic prescribing are: patient expectations, an important barrier which is surmountable; prescribing practices of medical colleagues, cultural memes and professional etiquette; and uncertainty of diagnosis coupled with patient expectations for antibiotics exert prescribing pressure on GPs. Conclusion: Patient expectation for antibiotics is the dominant modifiable factor influencing GP antibiotic prescribing behaviours. Key challenges to prudent antibiotic prescribing can be overcome through upskilling GPs to manage patient expectations efficaciously, and through two new emphases for public health campaigns—consumers have the power to reduce the use of antibiotics and the GP as a wise advocate for the patient.