We present an efficient and accurate computational approach to study phase-coherent quantum transport in molecular and nanoscale electronics. We formulate a Green’s-function method in the recently developed ab initio nonorthogonal quasiatomic orbital basis set within the Landauer-Büttiker formalism. These quasiatomic orbitals are efficiently and robustly transformed from Kohn-Sham eigenwave functions subject to the maximal atomic-orbital similarity measure. With this minimal basis set, we can easily calculate electrical conductance using Green’s-function method while keeping accuracy at the level of plane-wave density-functional theory. Our approach is validated in three studies of two-terminal electronic devices, in which projected density of states and conductance eigenchannel are employed to help understand microscopic mechanism of quantum transport. We first apply our approach to a seven-carbon atomic chain sandwiched between two finite crosssectioned Al(001) surfaces. The emergence of gaps in the conductance curve originates from the selection rule with vanishing overlap between symmetry-incompatible conductance eigenchannels in leads and conductor. In the second application, a (4,4) single-wall carbon nanotube with a substitutional silicon impurity is investigated. The complete suppression of transmission at 0.6 eV in one of the two conductance eigenchannels is attributed to the Fano antiresonance when the localized silicon impurity state couples with the continuum states of carbon nanotube. Finally, a benzene-1,4-dithiolate molecule attached to two Au(111) surfaces is considered. Combining fragment molecular orbital analysis and conductance eigenchannel analysis, we demonstrate that conductance peaks near the Fermi level result from resonant tunneling through molecular orbitals of benzene- 1,4-dithiolate molecule. In general, our conductance curves agree very well with previous results obtained using localized basis sets while slight difference is observed near the Fermi level and conductance edges.