In energy conversion techniques, two-dimensional (2D) thermoelectric materials with high performance are strongly required. This study scrutinizes the electronic and thermoelectric properties of 2D single-layer (1L) ZrTeSe4 based on first-principles calculations combined with Boltzmann transport theory. First-principles molecular dynamics simulations and phonon calculations confirm the thermodynamic stability of 1L-ZrTeSe4. Furthermore, the electron mobility of 1L-ZrTeSe4 is calculated to be ∼5706 cm2 V-1 s-1, which is much higher than that of the typical 2D semiconducting materials. Intriguingly, the calculated lattice thermal conductivity of 1L-ZrTeSe4 is found to be 3.16 W m-1 K-1 at room temperature, which is relatively smaller than that of 2D transition metal dichalcogenides. The maximum figure of merit ZT of 1L-ZrTeSe4 at 900 K is ∼0.8 for both p- and n-type doping at optimal carrier concentrations. As ZT could be improved through the manipulation of its electronic structure, this is an important clue indicating the enormous potential of 1L-ZrTeSe4 in thermoelectric application.