Non-invasive prenatal testing (NIPT) to detect fetal aneuploidy by sequencing the cell-free DNA (cfDNA) in maternal plasma is being broadly adopted. To detect fetal aneuploidies from maternal plasma, where fetal DNA is mixed with far-larger amounts of maternal DNA, NIPT requires a minimum fraction of the circulating cfDNA to be of placental origin, a level which is usually attained beginning at 10 weeks gestational age. We present an approach that leverages the arrangement of alleles along homologous chromosomes—also known as chromosomal phase—to make NIPT analyses more conclusive. We validate our approach with in silico simulations, then re-analyze data from a pregnant mother who, due to a fetal DNA fraction of 3.4%, received an inconclusive aneuploidy determination through NIPT. We find that the presence of a trisomy 18 fetus can be conclusively inferred from the patient’s same molecular data when chromosomal phase is incorporated into the analysis. Key to the effectiveness of our approach is the ability of homologous chromosomes to act as natural controls for each other and the ability of chromosomal phase to integrate subtle quantitative signals across very many sequence variants. These results show that chromosomal phase increases the sensitivity of a common laboratory test, an idea that could also advance cfDNA analyses for cancer detection.