This paper considers the sequential design of remedial control actions in response to system anomalies for the ultimate objective of preventing blackouts. A physics-guided reinforcement learning (RL) framework is designed to identify effective sequences of real-time remedial look-ahead decisions accounting for the long-term impact on the system's stability. The paper considers a space of control actions that involve both discrete-valued transmission line-switching decisions (line reconnections and removals) and continuous-valued generator adjustments. To identify an effective blackout mitigation policy, a physics-guided approach is designed that uses power-flow sensitivity factors associated with the power transmission network to guide the RL exploration during agent training. Comprehensive empirical evaluations using the open-source Grid2Op platform demonstrate the notable advantages of incorporating physical signals into RL decisions, establishing the gains of the proposed physics-guided approach compared to its black box counterparts. One important observation is that strategically~\emph{removing} transmission lines, in conjunction with multiple real-time generator adjustments, often renders effective long-term decisions that are likely to prevent or delay blackouts.