The main objective of this study was to assess the aspects of health-related quality of life (QOL) in patients with ankylosing spondylitis (AS) and to explore the disease-related parameters influencing it. One hundred patients with AS according to New York Classification criteria were recruited in this cross-sectional study. The Medical Outcomes Study Short Form 36 Health Survey (SF-36) was used to assess health-related QOL. Assessment criteria included the evaluation of disease activity (Bath Ankylosing Spondylitis Disease Activity index [BASDAI]), global well-being (Bath Ankylosing Spondylitis Global Index [BASGI]), enthesitis (Mander enthesis index [MEI]), functional status (Bath Ankylosing Spondylitis Functional Index [BASFI]); metrology (Bath Ankylosing Spondylitis Metrology Index [BASMI]) and radiographic damage (Bath Ankylosing Spondylitis Radiologic Index [BASRI]). In this study, males comprised 67% of the subjects; mean age was 38 ± 13 years and mean disease duration was 9.5 ± 6.8 years. Among these patients, 52% had hip involvement. Our patients had a moderately active disease and severe functional disability. All domains of SF-36 were deteriorated with low scores. The SF-36 subgroups most affected were role limitation (18.8 ± 28.1), role emotional (19.4 ± 35), general health (44.9 ± 20.3) and vitality (38.0 ± 18.2). Lower scores of SF-36 had good statistically significant correlations with altered functional status (BASFI), worse general well-being (BASGI), altered metrology (BASMI); and moderate correlations with high disease activity (BASDAI), important radiological damage (BASRI); restricted chest expansion and prolonged morning stiffness (p < 0.001). This study states that health-related QOL in Moroccan patients with AS is damaged in a significant way. Mental as well as physical aspects were affected. Functional disability, patient's well-being, metrology and disease activity are the main factors associated with deteriorating domains of QOL in AS. Recognizing complicated relationships between clinical measures and QOL in patients with AS can help us to develop further management strategies to improve their QOL.