The development of noisy intermediate-scale quantum (NISQ) devices has extended the scope of executable quantum circuits with high-fidelity single- and two-qubit gates. Equipping NISQ devices with three-qubit gates will enable the realization of more complex quantum algorithms and efficient quantum error correction protocols with reduced circuit depth. Several three-qubit gates have been implemented for superconducting qubits, but their use in gate synthesis has been limited due to their low fidelity. Here, using fixed-frequency superconducting qubits, we demonstrate a high-fidelity iToffoli gate based on two-qubit interactions, the so-called cross-resonance effect. As with the Toffoli gate, this three-qubit gate can be used to perform universal quantum computation. The iToffoli gate is implemented by simultaneously applying microwave pulses to a linear chain of three qubits, revealing a process fidelity as high as 98.26(2)%. Moreover, we numerically show that our gate scheme can produce additional three-qubit gates which provide more efficient gate synthesis than the Toffoli and iToffoli gates. Our work not only brings a high-fidelity iToffoli gate to current superconducting quantum processors but also opens a pathway for developing multi-qubit gates based on two-qubit interactions.