Background: This study aimed to investigate the levels of anxiety, depression, and quality of life among parents of children with autism spectrum disorder. It also compared the difference in these levels between mothers and fathers. Additionally, it quantifies the association between parental anxiety, depression, and quality of life, with various sociodemographic factors. Methods: This analytical, cross-sectional study was carried out between June and December 2022. An online questionnaire was completed by a sample of 394 parents of children with ASD (autism spectrum disorder) residing in Saudi Arabia. Three scales were used to assess depression, anxiety, and quality of life (QoL), respectively: Patient Health Questionnaire 9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), and World Health Organization Quality of Life—Brief Version (WHOQOL-BREF). Results: Most parents (70.8%) were mothers with an average age of 39 years, typically ranging from 30 to 48 years. Parents’ overall quality of life was 57.72 out of 100, indicating moderate satisfaction. Anxiety levels showed that 32% had mild, 17.8% moderate, and 14.7% severe anxiety. Similarly, depression levels revealed that 34.5% had minimal, 32.2% mild, and 18% moderate depression. Higher anxiety and depression scores were linked to a lower perceived QoL (quality of life). Moreover, the socioeconomic status index (SESi) was significantly and positively correlated with higher depression and lower quality of life. Conclusions: Autism Spectrum Disorder imposes a strain on parents of the autistic child. The responsibilities linked to the disability amplify the occurrence of depression and anxiety among parents, leading to a diminished quality of life.