Objective GREB1L has been linked prenatally to Potter's sequence, as well as less severe anomalies of the kidney, uterus, inner ear, and heart. The full phenotypic spectrum is unknown. The purpose of this study was to characterize known and novel pre‐ and postnatal phenotypes associated with GREB1L. Methods We solicited cases from the Fetal Sequencing Consortium, screened a population‐based genomic database, and conducted a comprehensive literature search to identify disease cases associated with GREB1L. We present a detailed phenotypic spectrum and molecular changes. Results One hundred twenty‐seven individuals with 51 unique pathogenic or likely pathogenic GREB1L variants were identified. 24 (47%) variants were associated with isolated kidney anomalies, 19 (37%) with anomalies of multiple systems, including one case of hypoplastic left heart syndrome, five (10%) with isolated sensorineural hearing loss, two (4%) with isolated uterine agenesis; and one (2%) with isolated tetralogy of Fallot. Conclusion GREB1L may cause complex congenital heart disease (CHD) in humans. Clinicians should consider GREB1L testing in the setting of CHD, and cardiac screening in the setting of GREB1L variants. Key points What is Already Known? GREB1L is associated prenatally with Potter's sequence, and postnatally with less severe anomalies of the kidney, uterus, inner ear, and heart. Known cardiac anomalies are aortic stenosis and ventricular hypertrophy. What does this Study Add? We identified complex congenital heart disease (CHD) associated with GREB1L. Clinicians should consider GREB1L testing in the setting of CHD, particularly outflow tract anomalies. Clinicians should consider pre‐ and postnatal screening for cardiac anomalies in the setting of GREB1L variants.