Key points Airway hyper‐responsiveness in asthma is driven by excessive contraction of airway smooth muscle cells (ASMCs). Agonist‐induced Ca2+ oscillations underlie this contraction of ASMCs and the magnitude of this contraction is proportional to the Ca2+ oscillation frequency. Sustained contraction and Ca2+ oscillations require an influx of extracellular Ca2+, although the mechanisms and pathways mediating this Ca2+ influx during agonist‐induced ASMC contraction are not well defined. By inhibiting store‐operated calcium entry (SOCE) or voltage‐gated Ca2+ channels (VGCCs), we show that SOCE, rather than Ca2+ influx via VGCCs, provides the major Ca2+ entry pathway into ASMCs to sustain ASMCs contraction and Ca2+ oscillations. SOCE may therefore serve as a potential target for new bronchodilators to reduce airway hyper‐responsiveness in asthma. Asthma is characterized by airway hyper‐responsiveness: the excessive contraction of airway smooth muscle. The extent of this airway contraction is proportional to the frequency of Ca2+ oscillations within airway smooth muscle cells (ASMCs). Sustained Ca2+ oscillations require a Ca2+ influx to replenish Ca2+ losses across the plasma membrane. Our previous studies implied store‐operated calcium entry (SOCE) as the major pathway for this Ca2+ influx. In the present study, we explore this hypothesis, by examining the effects of SOCE inhibitors (GSK7975A and GSK5498A) as well as L‐type voltage‐gated Ca2+ channel inhibitors (nifedipine and nimodipine) on airway contraction and Ca2+ oscillations and SOCE‐mediated Ca2+ influx in ASMCs within mouse precision‐cut lung slices. We found that both GSK7975A and GSK5498A were able to fully relax methacholine‐induced airway contraction by abolishing the Ca2+ oscillations, in a manner similar to that observed in zero extracellular Ca2+ (Ca2+e). In addition, GSK7975A and GSK5498A inhibited increases in intracellular Ca2+ (Ca2+i) in ASMCs with depleted Ca2+‐stores in response to increased Ca2+e, demonstrating a response consistent with the inhibition of SOCE. However, GSK7975A and GSK5498A did not reduce Ca2+ release via IP3 receptors stimulated with IP3 released from caged‐IP3. By contrast, nifedipine and nimodipine only partially reduced airway contraction, Ca2+ oscillation frequency and SOCE‐mediated Ca2+ influx. These data suggest that SOCE is the major Ca2+ influx pathway for ASMCs with respect to sustaining agonist‐induced airway contraction and the underlying Ca2+ oscillations. The mechanisms of SOCE may therefore form novel targets for new bronchodilators. Key points Airway hyper‐responsiveness in asthma is driven by excessive contraction of airway smooth muscle cells (ASMCs). Agonist‐induced Ca2+ oscillations underlie this contraction of ASMCs and the magnitude of this contraction is proportional to the Ca2+ oscillation frequency. Sustained contraction and Ca2+ oscillations require an influx of extracellular Ca2+, although the mechanisms and pathways mediating this Ca2+ influx during agonist‐induced ASMC contraction are not well defined. By inhibiting store‐operated calcium entry (SOCE) or voltage‐gated Ca2+ channels (VGCCs), we show that SOCE, rather than Ca2+ influx via VGCCs, provides the major Ca2+ entry pathway into ASMCs to sustain ASMCs contraction and Ca2+ oscillations. SOCE may therefore serve as a potential target for new bronchodilators to reduce airway hyper‐responsiveness in asthma.