Gyres and seiches are two prominent features of lakes. Gyres largely transport sediments, nutrients, and algae in the horizontal direction. Seiches, on the other hand, can contribute to the vertical mixing in lakes. Theoretical analysis, statistical methods, and numerical models are used to investigate gyres and seiches in Lake Okeechobee, the largest subtropical/tropical lake in North America. The lake has a 1,730-km² surface water area, a typical length of more than 50 km, and a mean depth of 3.2 m. Both the Empirical Orthogonal Function (EOF) method and the numerical model results indicated that lake circulation is typically dominated by a two-gyre pattern, especially in the winter. The northwest wind or southeast wind leads to a cyclone (a counterclockwise rotation gyre) in the southwest and an anticyclone (a clockwise rotation gyre) in the northeast. Because the mean velocity field in the lake is very weak, the first two EOF modes play an important role in lake transport. The mechanism of gyre formation in the lake is clearly explained in a theoretical analysis. Power spectra analysis on measured and modeled water elevations at four stations revealed that Lake Okeechobee has a seiche signal of 5 hours or so. The seiche range is typically around 10 cm. Results from the theoretical analysis, power spectral analysis, and numerical modeling all agree with each other very well. The findings in this study should be useful to understand the lake processes, to guide field data collection programs, and to assist decision making on lake management.