An experimental study is described on the fracture toughness and micro-mechanisms associated with the initiation and propagation of cracks in metallic nickel containing marked gradients in grain size, ranging from ∼30 nm to ∼4 μm. Specifically, cracks are grown in a gradient structured (GS) nickel with grain-size gradient ranging from the coarse macro-scale to nano-scale (CG → NG) and vice versa (NG → CG), with the measured crack-resistance R-curves compared to the corresponding behavior in uniform nano-grained (NG) and coarse-grained (CG) materials. It is found that the gradient structures display a much-improved combination of high strength and toughness compared to uniform grain-sized materials. However, based on J-integral measurements in the gradient materials, the crack-initiation toughness is far higher for cracks grown in the direction of the coarse-to-nano grained gradient than vice versa, a result which we ascribe primarily to excessive crack-tip blunting in the coarse-grained microstructure. Both gradient structures, however, display marked rising R-curve behavior with exceptional crack-growth toughnesses exceeding 200 MPa.m½.