Abstract At redshift z = 4.618, GRB 220101A is the most distant gamma-ray burst (GRB) detected by Fermi/LAT to date. It is also a very energetic event, with an equivalent isotropic energy of 3.6 × 10 54 erg. We jointly analyzed the Fermi/GBM and LAT observations of GRB 220101A with two independent approaches and found a significant spectral break at sub-100 MeV energies during the prompt emission. The fast variability of the emission suggests that this spectral attenuation is caused by internal opacity to pair creation. Regardless of the nature of the emission processes assumed in the spectral analysis, we infer a moderate value for the jet Lorentz factor, Γ ∼ 110, and find that all of the high-energy emission was produced above and near the photosphere, at a distance of ∼10 14 cm from the central engine. We compare these results with the four other LAT-detected GRBs with similar properties.