Background: While several acoustic voice metrics are available for clinical voice assessment, there remains a significant need for reliable and ecologically valid tools. The Acoustic Voice Quality Index version 03.01 (AVQI-3) and Acoustic Breathiness Index (ABI) hold potential due to their comprehensive assessment approach, incorporating diverse voice aspects. However, these tools still need to be validated in English-speaking populations. Methods: This study assessed the discriminatory accuracy and validity of AVQI-3 and ABI in 197 participants, including 148 with voice disorders. Voice samples were collected, followed by AVQI-3 and ABI calculations. Additionally, auditory-perceptual assessments were conducted by a panel of speech-language pathologists. Results: AVQI-3 and ABI effectively identified disordered voice quality, evidenced by high accuracy (AUCs: 0.84, 0.89), sensitivity, and specificity (thresholds: AVQI-3 = 1.17, ABI = 2.35). Strong positive correlations were observed with subjective voice quality assessments (rs = 0.72, rs = 0.77, p < 0.001). Conclusions: The study highlights AVQI-3 and ABI as promising instruments for clinically assessing voice disorders in U.S. English speakers, underscoring their utility in clinical practice and voice research.