(1) Background: The aim of this research was to analyze factors associated with quality of life (QoL) and marital satisfaction in married family caregivers of patients with mental disorders. (2) Methods: A cross-sectional study was conducted in all community mental health services in Goiania municipality, Brazil, in 2016–2017. Married family caregivers of patients with severe and persistent mental disorders were recruited and their QoL and marital satisfaction was assessed by using the World Health Organization Quality of Life Instrument Abbreviated version (WHOQOL-BREF) and Marital Satisfaction Scale. Multiple linear regressions were performed to identify factors associated with QoL and marital satisfaction. (3) Results: For 163 family caregivers, the psychological and environmental QoL domains presented the best and the worst scores, respectively. Factors independently associated with better QoL for caregivers were male caregiver, the younger age of a caregiver, >8 years of schooling, ≥5 years as a caregiver who performed physical activities, caregiver without chronic disease, and no patient’s crisis in the last 30 days. Factors independently associated with marital satisfaction of the caregiver were male caregiver, caregiver with >8 years of schooling, caregiver who received support by relatives to care for the patient, caregiver who performed physical activities, no patient’s crisis in the last 30 days, and patient hospitalization in the last six months; (4) Conclusions: The main predictor for marital satisfaction was support by relatives, and for QoL it was no patient’s crisis in the last 30 days.