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We define a class of zero-sum games with combinatorial structure, where the best response problem of one player is to maximize a submodular function. For example, this class includes security games played on networks, as well as the problem of robustly optimizing a submodular function over the worst case from a set of scenarios. The challenge in computing equilibria is that both players' strategy spaces can be exponentially large. Accordingly, previous algorithms have worst-case exponential runtime and indeed fail to scale up on practical instances. We provide a pseudopolynomial-time algorithm which obtains a guaranteed (1 - 1/e)^2-approximate mixed strategy for the maximizing player. Our algorithm only requires access to a weakened version of a best response oracle for the minimizing player which runs in polynomial time. Experimental results for network security games and a robust budget allocation problem confirm that our algorithm delivers near-optimal solutions and scales to much larger instances than was previously possible.