ABSTRACT Objective Pre‐eclampsia (PE) is a serious complication of pregnancy associated with maternal and fetal morbidity and mortality. As current prediction models have limitations and may not be applicable in resource‐limited settings, we aimed to develop a machine‐learning (ML) algorithm that offers a potential solution for developing accurate and efficient first‐trimester prediction of PE. Methods We conducted a prospective cohort study in Mexico City, Mexico to develop a first‐trimester prediction model for preterm PE (pPE) using ML. Maternal characteristics and locally derived multiples of the median (MoM) values for mean arterial pressure, uterine artery pulsatility index and serum placental growth factor were used for variable selection. The dataset was split into training, validation and test sets. An elastic‐net method was employed for predictor selection, and model performance was evaluated using area under the receiver‐operating‐characteristics curve (AUC) and detection rates (DR) at 10% false‐positive rates (FPR). Results The final analysis included 3050 pregnant women, of whom 124 (4.07%) developed PE. The ML model showed good performance, with AUCs of 0.897, 0.963 and 0.778 for pPE, early‐onset PE (ePE) and any type of PE (all‐PE), respectively. The DRs at 10% FPR were 76.5%, 88.2% and 50.1% for pPE, ePE and all‐PE, respectively. Conclusions Our ML model demonstrated high accuracy in predicting pPE and ePE using first‐trimester maternal characteristics and locally derived MoM. The model may provide an efficient and accessible tool for early prediction of PE, facilitating timely intervention and improved maternal and fetal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.