This paper proposes a high-gain disturbance observer (HDOB)-based controller for load frequency control (LFC) of power systems with multiple areas. The main goal of LFC problem is to maintain the frequency to its nominal value. The objective of this paper is to reject frequency variations due to abrupt load changes and diverse uncertainties (e.g., inertia and damping parameters, and interconnection topology, etc.) by employing the HDOB for the LFC. The simulation results demonstrate the effectiveness of the proposed HDOB-based LFC by showing that it successfully rejects frequency variations owing to load changes and frequency variations occurring in various locations in interconnected power systems. Besides, it is shown that the proposed LFC can eliminate frequency deviations although there are delays in transmission among the power systems with multiple areas.