Flame initiation from an ignition kernel is studied theoretically and numerically for different fuel (hydrogen, methane, and propane)/oxygen/helium/ argon mixtures by using a spherical flame. The objectives are to find the controlling length scale for flame initiation in a quiescent mixture and to reveal its relationship with the minimum ignition energy. The results show that, different from the flame thickness or flame ball radius, there is a critical flame radius that controls flame initiation. The minimum ignition energy for successful flame initiation is found to be proportional to the volume defined by the critical flame radius. Furthermore, the preferential diffusion between heat and mass (Lewis number effect) is found to play an important role in affecting the critical flame radius and flame initiation. It is shown that the critical flame radius and the minimum ignition energy increase significantly with the increase of Lewis number. Therefore, for large molecular hydrocarbon fuels with low mass diffusivity, significantly larger ignition energy is needed to initiate successfully a self-sustained propagating premixed flame.