BACKGROUND: History-taking is crucial in medical training. However, current methods often lack consistent feedback and standardized evaluation and have limited access to standardized patient (SP) resources. Artificial intelligence (AI)-powered simulated patients offer a promising solution; however, challenges such as human-AI consistency, evaluation stability, and transparency remain underexplored in multicase clinical scenarios. OBJECTIVE: This study aimed to develop and validate the AI-Powered Medical History-Taking Training and Evaluation System (AMTES), based on DeepSeek-V2.5 (DeepSeek), to assess its stability, human-AI consistency, and transparency in clinical scenarios with varying symptoms and difficulty levels. METHODS: We developed AMTES, a system using multiple strategies to ensure dialog quality and automated assessment. A prospective study with 31 medical students evaluated AMTES's performance across 3 cases of varying complexity: a simple case (cough), a moderate case (frequent urination), and a complex case (abdominal pain). To validate our design, we conducted systematic baseline comparisons to measure the incremental improvements from each level of our design approach and tested the framework's generalizability by implementing it with an alternative large language model (LLM) Qwen-Max (Qwen AI; version 20250409), under a zero-modification condition. RESULTS: A total of 31 students practiced with our AMTES. During the training, students generated 8606 questions across 93 history-taking sessions. AMTES achieved high dialog accuracy: 98.6% (SD 1.5%) for cough, 99.0% (SD 1.1%) for frequent urination, and 97.9% (SD 2.2%) for abdominal pain, with contextual appropriateness exceeding 99%. The system's automated assessments demonstrated exceptional stability and high human-AI consistency, supported by transparent, evidence-based rationales. Specifically, the coefficients of variation (CV) were low across total scores (0.87%-1.12%) and item-level scoring (0.55%-0.73%). Total score consistency was robust, with the intraclass correlation coefficients (ICCs) exceeding 0.923 across all scenarios, showing strong agreement. The item-level consistency was remarkably high, consistently above 95%, even for complex cases like abdominal pain (95.75% consistency). In systematic baseline comparisons, the fully-processed system improved ICCs from 0.414/0.500 to 0.923/0.972 (moderate and complex cases), with all CVs ≤1.2% across the 3 cases. A zero-modification implementation of our evaluation framework with an alternative LLM (Qwen-Max) achieved near-identical performance, with the item-level consistency rates over 94.5% and ICCs exceeding 0.89. Overall, 87% of students found AMTES helpful, and 83% expressed a desire to use it again in the future. CONCLUSIONS: Our data showed that AMTES demonstrates significant educational value through its LLM-based virtual SPs, which successfully provided authentic clinical dialogs with high response accuracy and delivered consistent, transparent educational feedback. Combined with strong user approval, these findings highlight AMTES's potential as a valuable, adaptable, and generalizable tool for medical history-taking training across various educational contexts.