Host antiviral proteins engage in evolutionary arms races with viruses, in which both sides rapidly evolve at interaction interfaces to gain or evade immune defense . For example, primate TRIM5α uses its rapidly evolving ‘ v1 ’ loop to bind retroviral capsids, and single mutations in this loop can dramatically improve retroviral restriction . However, it is unknown whether such gains of viral restriction are rare, or if they incur loss of pre-existing function against other viruses . Using deep mutational scanning, we comprehensively measured how single mutations in the TRIM5α v1 loop affect restriction of divergent retroviruses . Unexpectedly, we found that the majority of mutations increase weak antiviral function . Moreover, most random mutations do not disrupt potent viral restriction, even when it is newly acquired via a single adaptive substitution . Our results indicate that TRIM5α ’ s adaptive landscape is remarkably broad and mutationally resilient, maximizing its chances of success in evolutionary arms races with retroviruses.