Nanostructured Cu/Fe multilayers on Si (1 1 0) and Si (1 0 0) substrates were prepared by magnetron sputtering, with individual layer thicknesses h varying from 0.75 to 200 nm. The growth orientation relationships between Cu and Fe at the interfaces were determined to be of the Kurdjumov-Sachs and Nishiyama-Wasserman type. Nanoscale columnar grains in Fe, with an average grain size of 11-23 nm, played a dominant role in the strengthening mechanism when h ≥ 50 nm. At smaller h the hardness of Cu/Fe multilayers with (1 0 0) texture approached a peak value, followed by softening due to the formation of fully coherent interfaces. However, abundant twins were observed in Cu/Fe films with (1 1 1) texture when h = 0.75 nm, which led to the retention of high hardness in the multilayers.