The photon's frequency degree of freedom, being compatible with mature telecom infrastructure, offers large potential for the stable and controllable realization of photonic quantum processing applications such as the quantum internet. The Hong–Ou–Mandel effect, as a two-photon interference phenomenon, serves as a central building block for such frameworks. A key element yet missing to enable meaningful frequency-based implementations as well as scalability in the number of processed photons, is the demonstration of the Hong–Ou–Mandel effect between independently created photons of different frequencies. The experimental implementation of bosonic and fermionic frequency domain Hong–Ou–Mandel interference between independently generated single photons is reported here, with measured visibilities of 74.31% ± 3.56% and 86.44% ± 8.27%, respectively. This is achieved through a scalable photonic frequency circuit that creates two post-selected pure single photons, which undergo frequency mixing at an electro-optic phase modulator. The system is on-the-fly reconfigurable allowing to probe bosonic and fermionic Hong–Ou–Mandel interference in the same experimental setup. The work demonstrates the versatility of frequency domain processing and its scalability toward higher photon numbers, which enables new quantum gate concepts as well as the establishment of frequency-based large-scale quantum networks. © 2021 The Authors. Laser & Photonics Reviews published by Wiley-VCH GmbH