Electroencephalogram (EEG) is one of the most powerful tools that offer valuable information related to different abnormalities in the human brain. One of these abnormalities is the epileptic seizure. A framework is proposed for detecting epileptic seizures from EEG signals recorded from normal and epileptic patients. The suggested approach is designed to classify the abnormal signal from the normal one automatically. This work aims to improve the accuracy of epileptic seizure detection and reduce computational costs. To address this, the proposed framework uses the 54-DWT mother wavelets analysis of EEG signals using the Genetic algorithm (GA) in combination with other four machine learning (ML) classifiers: Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Artificial Neural Network (ANN), and Naive Bayes (NB). The performance of 14 different combinations of two-class epilepsy detection is investigated using these four ML classifiers. The experimental results show that the four classifiers produce comparable results for the derived statistical features from the 54-DWT mother wavelets; however, the ANN classifier achieved the best accuracy in most datasets combinations, and it outperformed the other examined classifiers.