Chronic loneliness is associated with a range of mental health difficulties. Previous theory and research indicate that psychological interventions show promise for reducing loneliness, however, there have been no systematic reviews or meta-analyses to ascertain the efficacy of these interventions across the lifespan. The aim of this study was to synthesise, meta-analyse and explore the heterogeneity in RCTs of psychological interventions for loneliness in order to establish their efficacy. Five databases (Ovid Embase, Ovid Medline, PsycINFO, Web of Science and CINAHL) were systematically searched in order to identify relevant studies. Included studies were required to be peer-reviewed RCTs examining psychological interventions for loneliness. Two independent coders examined the abstracts of the 3973 studies and 103 full texts, finding 31 studies that met inclusion criteria, 28 of which contained sufficient statistical information to be included in the meta-analysis. The quality of included studies was assessed using the Cochrane Risk of Bias Tool. The 31 studies (N = 3959) that were included in the systematic review were conducted with participants from a diverse range of cultures, age groups and populations. The interventions were of mixed quality and were mostly face to face, group-based and delivered weekly. The most common type of intervention was Cognitive Behavioural Therapy (CBT). 28 studies (N = 3039) were included in a meta-analysis which found that psychological interventions significantly reduced loneliness compared to control groups, yielding a small to medium effect size (g = 0.43). Subgroup analysis and meta-regressions were conducted in order to explore heterogeneity and found that type of psychological intervention was approaching significance as a moderator of the effectiveness of psychological interventions for loneliness. In conclusion, psychological interventions for loneliness across the lifespan are effective. This finding should inform policy makers, researchers and clinicians going forward, especially in the context of increased loneliness due to the COVID-19 pandemic. There was considerable heterogeneity in the effectiveness of the interventions, suggesting that future research should also explore what works for whom and consider personalising psychological treatment.