Objectives: This systematic review aimed to quantify differences in loneliness levels between autistic and neurotypical samples and investigate the association between loneliness and mental health in autistic individuals. Methods: Three meta-analyses were conducted. Studies were methodologically appraised using established tools. Results: Overall, 39 studies were included. The majority of these achieved moderate methodological quality ratings. The primary meta-analysis (N = 23) found autistic samples reported higher loneliness compared with neurotypical samples (Hedges' g = 0.89). The meta-analyses on the associations between loneliness and anxiety (N = 14) and depression (N = 11) in autistic samples found significant pooled correlations (r = 0.29 and r = 0.48, respectively). Conclusions: This review highlights numerous limitations within current autism and loneliness research. Nevertheless, loneliness in autism merits targeted clinical and research attention.