Genetic defects are a major cause of pregnancy loss, leading to fetal death or elective abortion due to congenital anomalies. This study evaluates the effectiveness of trio exome sequencing (ES) in identifying genetic causes of pregnancy loss. Trio ES was used as a first-tier genetic test on 193 cases of pregnancy loss to detect both chromosomal abnormalities and small variants potentially linked to fetal death and anomalies. The pathogenicity of identified variants was assessed, and the diagnostic yield was analyzed. Trio ES provided an overall diagnostic yield of 24% (47/193) across this cohort, with a similar positive rate observed in fetal death (26%, 12/45) and elective abortion (23%, 35/148) groups. Among diagnosed cases, 45% (21/47) were attributed to chromosomal abnormalities, while 55% (26/47) were caused by small variants. This suggests that ES more than doubled the positive rates compared to traditional methods such as karyotyping and chromosomal microarray analysis. Notably, chromosomal abnormalities were the primary cause of fetal death (75%, 9/12), whereas small variants were more prevalent in elective abortion cases (68%, 24/35), particularly those with central nervous and skeletal anomalies. Additional candidate variants were identified in 35 inconclusive cases (18%), potentially further increasing the detection rate. This study highlights the value of trio ES in diagnosing genetic causes of pregnancy loss. Implementing it as a first-tier test can significantly enhance our understanding of fetal death and anomalies, therefore facilitating informed future pregnancy management.