Objective The objective was to determine sex differences in disease outcomes in recent axial spondyloarthritis (SpA) over time. Methods We analyzed the first 6 years of follow-up of the prospective French multicenter DESIR cohort. Patients analyzed had <3 years of disease, were naive to disease-modifying antirheumatic drugs, and fulfilled the Assessment of SpondyloArthritis international Society classification criteria for axial SpA. Disease activity (Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C-reactive protein [CRP] level), patient global assessment (PtGA), CRP level, and radiographic sacroiliitis were compared between men and women (self-reported sex) by linear and logistic mixed-effects models. Models were created for trajectories of disease activity over 6 years in men and women, using k-means. Results Of 494 patients analyzed (mean ± SD age 31.9 ± 7.5 years, symptoms duration 20.7 ± 11.7 months), 50.4% were men. Over 6 years of follow-up, both men and women showed clear improvements in ASDAS-CRP, PtGA, and CRP level. Women had higher ASDAS-CRP and PtGA over time compared to men (both P < 0.0001) with overall similar CRP levels (P = 0.089), whereas structural damage increased more in men (P < 0.0001). One-third of both men (33%) and women (34%) belonged to persistent high/very high disease activity trajectories, but ASDAS-CRP was globally higher in women in these trajectories. Conclusion In early axial SpA, clinical outcomes (disease activity and symptoms) were worse in women than men over 6 years of follow-up, whereas CRP was similar and structural damage was more frequent in men. Although similarly distributed, disease activity scores were higher in women in high/very high disease activity trajectories. Sex appears to be an important contextual factor in axial SpA.