Parastic weeds such as Striga have led to significant losses in agricultural productivity worldwide. These weeds use the plant hormone strigolactone as a germination stimulant. Strigolactone signaling involves substrate binding and hydrolysis followed by a large conformational change of the receptor to a “closed” or “active” state that is able to associate with a downstream signaling partner MAX2/D3. The crystal structure of the active and inactive AtD14 receptor have helped in elucidating the structural changes involved in activation. However, the mechanism by which the receptor activates remains unknown. The ligand dependence of AtD14 activation has been disputed by mutagenesis studies showing that enzymatically inactive receptors are able to form a complex with MAX2 proteins. Furthermore, activation differences between strigolactone receptor in Striga, ShHTL7 and textitAtD14 could contribute to the high sensitivity to strigolactones exhibited by parasitic plants. Using molecular dynamics simulations, we demonstrate that both AtD14 and ShHTL7 could adopt an active conformation in absence of ligand. However, the ShHTL7 receptor exhibits higher population in the inactive apo state as compared to the AtD14 receptor. We demonstrate that this difference in inactive state population is caused by sequence differences between their D-loops and its interactions with the catalytic histidine that prevents full binding pocket closure in ShHTL7. These results indicate that hydrolysis of a strigolactone ligand would enhance the active state population by destabilizing the inactive state in ShHTL7 as compared to AtD14. We also show that the mechanism of activation is more concerted in AtD14 than in ShHTL7 and that the main barrier to activation in ShHTL7 is closing of the binding pocket.