Significance The simultaneous flow of multiple fluid phases through a porous solid occurs in many natural and industrial processes—for example, rainwater infiltrates into soil by displacing air, and carbon dioxide is stored in deep saline aquifers by displacing brine. It has been known for decades that wetting—the affinity of the solid to one of the fluids—can have a strong impact on the flow, but the microscale physics and macroscopic consequences remain poorly understood. Here, we study this in detail by systematically varying the wetting properties of a microfluidic porous medium. Our high-resolution images reveal the fundamental control of wetting on multiphase flow, elucidate the inherently 3D pore-scale mechanisms, and help explain the striking macroscopic displacement patterns that emerge.