Objective: This study aimed to evaluate the prevalence of vaccine hesitancy among patients with chronic inflammatory rheumatic diseases (CIRD) in comparison to those with common mechanical pathologies and to explore the factors influencing vaccine hesitancy. Methods: This case-control study in Morocco compared patients with chronic inflammatory rheumatic diseases (CIRD) and those with degenerative mechanical pathologies. Data were collected via questionnaires from December 2021 to December 2022, assessing demographics, medical history, and vaccine hesitancy. Differences between groups were assessed using chi-square tests and t-tests. A logistic regression model was used to identify factors associated with vaccine hesitancy. Results: One-hundred-fifteen patients with chronic inflammatory rheumatic diseases (CIRD) were included (median age 49 years, 75.7% women). The majority had rheumatoid arthritis (54.9%) and were on biological treatment (63.2%). About 83% were vaccinated against COVID-19, with 70% reporting no post-vaccination adverse events. Vaccine hesitancy was high (68%), primarily due to fear of adverse events (57.1%). Age was negatively associated with reluctance, but no association was found with gender, education, or CIRD type. In the control group (74 patients, median age 59.5 years, 87.8% women), 92% were vaccinated. Vaccine hesitancy was 74.3%, mainly due to fear of adverse events (59.6%). Univariate and multivariate analyses showed a significant negative association between age and vaccine hesitancy (OR = 0.905, p = 0.023), with no associations to gender or education. Conclusions: High COVID-19 vaccine hesitancy was observed in both patient groups, mainly due to concerns about side effects, worsening conditions, low trust in the healthcare system, and insufficient information. Age was also a factor, with younger individuals showing higher reluctance. Increasing awareness is essential to build trust and promote vaccination for herd immunity.