Background: To explore the effectiveness of standardized first-trimester ultrasound screening (FTS) in detecting fetal structural abnormalities in a non-selective population. Methods: A retrospective study was performed on 7523 fetuses (6376 single and 569 twin pregnancies) who underwent FTS between 11 and 13{}^{+6} weeks’ gestation. All fetuses received anatomy scans using a standardized protocol. Results: 147 fetuses (133 single and 7 twin pregnancies) were lost to follow up. Of the remaining 7376 fetuses, 119 (1.61%, 119/7376) developed structural malformations, with 64 cases (53.8%, 64/119) identified during the first trimester. The remaining cases were detected during the second trimester (24.4%, 29/119), the third trimester (1.68%, 2/119), and postnatally (20.2%, 24/119). There were 4 cases of suspected ventricular septal defect (VSD) by FTS, which were later confirmed to be normal. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for FTS were 54.2%, 99.9%, 94.1%, and 99.3%, respectively. Forty eight fetuses, accounting for 10.6% of the total (452), with thickened nuchal translucency (NT) (above the 95th percentile) showed structural malformations. This was significantly higher than the prevalence of structural abnormalities found in fetuses with normal NT (1.0%, 71/6924) (p 0.01). Conclusions: Standardized FTS is highly effective in detecting fetal structural malformations early, with impressive specificity, PPV, and NPV. Increased NT suggests detailed anatomy screening and helps guide treatment. However, while standardized FTS is an invaluable tool, it cannot fully replace the sensitivity of second- and third-trimester ultrasound screening. Clinical Trial Registration: The study was registered at https://www.chictr.org.cn (registration number ChiCTR-SOC-17010976).