Hearing loss (HL) is the most common sensory deficit in humans and a major global health problem, with severe consequences for affected individuals and society. Genetic causes account for >50% of sensorineural HL, which often presents as a HL syndrome in combination with further deficits. Usher syndrome type 1B (USH1B) is one of the most severe HL syndromes with congenital, profound deafness, vestibular areflexia leading to imbalance and vertigo, and progressive vision loss. Current treatment options are limited to cochlea implants, which can partially address HL, while vestibular hypofunction and blindness remain unaddressed. Pathogenic variants within the MYO7A gene are causative for USH1B, proposing gene therapy as a potentially curative treatment option. Therefore, a state-of-the-art lentiviral (LV) vector platform was used to deliver the large 6.6 kB MYO7A cDNA. Application of a dTomato reporter vector to normal-hearing mice demonstrated that our platform efficiently transduced inner ear cells, incl. cochlear and vestibular hair cells as the main USH1B target cells. A therapeutic LV vector expressing MYO7A and dTomato (LV.MYO7A) did not negatively affect hearing or balance function in normal-hearing mice. Strikingly, in homozygous Shaker-1 mice, an USH1B mouse model carrying a Myo7a point mutation, LV.MYO7A gene therapy strongly reduced the balance deficit and significantly improved hearing capacity. In heterozygous mutant mice, which were found to develop late-onset hearing loss, LV.MYO7A gene therapy completely rescued hearing to wild-type hearing thresholds. Thus, LV.MYO7A gene therapy constitutes the first treatment concept that addresses both the vestibular and the cochlear dysfunction in USH1B.