Recently, two-dimensional (2D) ternary layered telluride materials have attracted enormous attention due to their exotic electronic properties. Here, we propose two new monolayer 2D semiconductors Nb2SiTe4 and Nb2GeTe4, which show high dynamic, thermodynamic and mechanical stability. Nb2SiTe4 and Nb2GeTe4 have stable three-dimensional layered bulk counterparts, and monolayer Nb2SiTe4 and Nb2GeTe4 have low cleavage energies such that exfoliation of bulk material becomes a viable means for the preparation of mono- and few-layer materials. Indirect band gap of 0.80 eV and 0.63 eV have been revealed in monolayer Nb2SiTe4 and Nb2GeTe4. Acoustic phono-limited carrier mobilities are estimated, where monolayer Nb2SiTe4 exhibits high electron mobilities up to 1775 cm2 V−1 s−1 and 1222 cm2 V−1 s−1 along a and b directions, respectively. Analysis of mechanical properties reveals that 2D Nb2SiTe4 and Nb2GeTe4 are positive Poisson’s ratio materials with moderate Young’s moduli. The bonding characteristics have been investigated through electron localization function and Bader charges. Pronounced light absorption is predicted in the visible light and ultraviolet regions. These findings render 2D Nb2SiTe4 and Nb2GeTe4 attractive candidates for future nanoelectronics and optoelectronics.