Most EEG-based BCI systems make use of well-studied patterns of brain activity. However, those systems involve tasks that indirectly map to simple binary commands such as “yes” or “no” or require many weeks of biofeedback training. We hypothesized that signal processing and machine learning methods can be used to discriminate EEG in a direct “yes”/“no” BCI from a single session. Blind source separation (BSS) and spectral transformations of the EEG produced a 180-dimensional feature space. We used a modified genetic algorithm (GA) wrapped around a support vector machine (SVM) classifier to search the space of feature subsets. The GA-based search found feature subsets that outperform full feature sets and random feature subsets. Also, BSS transformations of the EEG outperformed the original time series, particularly in conjunction with a subset search of both spaces. The results suggest that BSS and feature selection can be used to improve the performance of even a “direct,” single-session BCI.