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Patients with ankylosing spondylitis (AS) may require biological therapy, particularly tumour necrosis factor (TNF) inhibitors, which are effective but increase the risk of tuberculosis (TB). Secukinumab, an interleukin-17A inhibitor, has not been linked to TB reactivation; however, its safety in the setting of active TB remains unclear. We report two patients with AS who developed active TB during long-term anti-TNF treatment. Both experienced disease flares while receiving anti-TB therapy and needed alternative biologic treatment. Secukinumab was started 2 months after initiating standard four-drug TB therapy and achieved rapid and sustained control of AS activity without compromising TB management. Both patients completed 9 months of anti-TB treatment without adverse events or TB reactivation during 1 year follow-up. These observations suggest that secukinumab may be a safe and effective therapeutic option for patients with AS with concomitant active TB when anti-TNF agents are contraindicated, though confirmation in larger studies is warranted.