Purpose: This study aimed to examine psychometric properties of a caregiver version of the well-established Functional Assessment of Cancer Therapy-General Scale (FACT-G) after conducting focus groups and obtaining expert input. Methods: We made minor wording modifications to the Patient FACT-G to enable caregivers to report how the illness affected their overall quality of life (QOL) and well-being on four subscales (physical, social, emotional, functional). We tested the acceptability, precision, factor structure, reliability and validity of the Caregiver FACT-G among partners of prostate cancer patients (N = 263) and caregivers (spouses, siblings, adult children) of patients with advanced cancer (breast, lung, colorectal, prostate) (N = 484) using data from two Randomized Clinical Trials (RCTs). Results: With a factor structure similar to the Patient FACT-G, Caregiver FACT-G was acceptable and precise in measuring caregiver QOL, with high inter-factor correlations and internal consistency reliability (Cronbach's alphas 0.81–0.91). The Caregiver FACT-G had strong convergent validity demonstrated by significant positive correlations with caregiver self-efficacy (0.25–0.63), dyadic communication (0.18–0.51), and social support (0.18–0.54) in both samples. It also had strong discriminant validity evidenced by significant inverse correlations with negative appraisal of caregiving (− 0.37 to − 0.69), uncertainty (− 0.28 to − 0.53), hopelessness (− 0.25 to − 0.60), and avoidant coping (− 0.26 to − 0.58) in both samples. Caregivers' baseline FACT-G scores were significantly associated with their physical (0.23) and mental well-being (0.54; 4-month follow-up) and their depression (− 0.69; 3-month follow-up), indicating strong predictive validity. Conclusion: This is the first study evaluating the psychometric properties of the Caregiver FACT-G. More psychometric testing is warranted, especially among caregivers of diverse sociocultural backgrounds.