Background: The psychological burden in people with inflammatory arthritis is substantial, yet little is known about the disease-related affect experienced by individuals with axial Spondyloarthritis (axial SpA). The aim of this study was to conduct a qualitative evidence synthesis and a review of social media to explore the emotional impact of living with axial SpA. Methods: We searched nine databases for studies reporting qualitative data about participants’ emotional experience of living with axial SpA. In addition, we searched social media platforms for posts from people with axial SpA based in the UK that offered insights into emotional responses to living with the condition. We employed a thematic approach to synthesise the data. Results: We included 27 studies (1314 participants; 72% men) in our qualitative evidence synthesis and developed seven descriptive themes from the data: 1) delayed diagnosis: a barrier to emotional wellbeing; 2) disruptive symptoms: a source of mood swings; 3) work disability: a loss of self-esteem; 4) obstacles in interpersonal relationships: a trigger of distress; 5) taking up exercise: personal pride or unwelcomed reminders; 6) anti-TNF therapy: hope reignited despite concerns and 7) a journey of acceptance: worry mixed with hope. Posts extracted from social media fora (537; 48% from women) for the most part supported the seven themes. One additional theme—COVID-19, uncertainty and anxiety during the pandemic, was developed, reflecting common emotions expressed during the UK’s first wave of the coronavirus pandemic. Conclusion: This study highlights a preponderance of negative affect experienced by people living with axial SpA, conditioned through existing and anticipated symptoms, failed expectations, and lost sense of self. Given the bidirectional relationships between negative emotions and inflammation, negative emotions and perceptions of pain, and the influence of affect in self-care behaviours, this finding has important implications for treatment and management of people with axial SpA.