In magnetic resonance (MR) images, detection of focal cortical dysplasia (FCD) lesion as a main pathological cue of epilepsy is challenging because of the variability in the presentation of FCD lesions. Existing algorithms appear to have sufficient sensitivity in detecting lesions but also generate large numbers of false-positive (FP) results. In this paper, we propose a multiple classifier fusion and optimization schemes to automatically detect FCD lesions in MR images with reduced FPs through constructing an objective function based on the F-score. Thus, the proposed scheme obtains an improved tradeoff between minimizing FPs and maximizing true positives. The optimization is achieved by incorporating the genetic algorithm into the work scheme. Hence, the contribution of weighting coefficients to different classifications can be effectively determined. The resultant optimized weightings are applied to fuse the classification results. A set of six typical FCD features and six corresponding Z-score maps are evaluated through the mean F-score from multiple classifiers for each feature. From the experimental results, the proposed scheme can automatically detect FCD lesions in 9 out of 10 patients while correctly classifying 31 healthy controls. The proposed scheme acquires a lower FP rate and a higher F-score in comparison with two state-of-the-art methods.