Many smooth muscle tissues display plateau-like electrical activity, where action potential (AP) duration dictates the duration of contraction. A plateau phase is a particularly prominent in the AP of human uterine smooth muscle (myometrium). The ionic conductances responsible for determining the amplitude and duration, and the rapid repolarization of the plateau in human myometrium are unknown. The cardiac AP also has a prominent plateau and the rapid current via hERG1 channels, Ikr, plays an important role in repolarization. hERG has been identified in a range of smooth muscle tissues. In the present study, we obtained human myometrium following caesarean delivery, having obtained informed written consent from the women. We recorded membrane potential and contraction simultaneously in strips of myometrium, and ion currents in smooth muscle cells isolated from the same tissue samples. hERG protein levels were determined using Western blotting. The hERG blockers dofetilide (1μM) and E-4031 caused a striking prolongation of the plateau phase of the AP and contraction, from 0.9±0.2 min to 2.8±0.2 min (a 2.9 fold increase, n=10, p<0.001). The hERG activator ICA-195574 reduced contraction duration to 53% (n=5). The hERG current in acutely isolated myometrial cells had a maximum amplitude of 3.6±0.4pA/pF and was blocked by dofetilide and E-4031. In tissues obtained from women in established labour, dofetilide increased AP duration from 2.8±0.1 to 3.6±0.1 (p=0.008, n=7), an increase of only 1.3 fold, and the maximum hERG current was reduced to 1.3±0.4pA/pF. While levels of the α pore-forming hERG subunit remained unchanged, levels of the β auxiliary subunit, which suppresses the hERG current, were increased 2.4 fold during labour (p<0.0001, n=12 in each group). As BMI increased, the effectiveness of dofetilide in prolonging AP duration was enhanced before (r2=0.89, n=22) and during (r2=0.68, n=18) labour, suggesting enhanced hERG expression/activity. Further investigation identified a small increase in the α subunit but a striking reduction in β subunit levels with increasing BMI (r2=0.70) in tissue from women in labour. Thus, hERG channels suppressed AP duration and contraction amplitude and duration before labour, facilitating quiescence. Then, changes in hERG channel function, via the β subunit, contribute to AP mechanisms that produce the powerful, sustained, well-spaced contractions typical of labour, and failure of this system likely contributes to the poor labour and increased incidence of caesarean delivery in many obese women. These results demonstrate the dynamic contribution of hERG channels, particularly the β subunit, to native smooth muscle cell function in physiology and pathology.