Complement activation modulates DC‐mediated T‐cell activation, but whether complement affects DC‐mediated priming of NK cells is unknown. Here, we demonstrated that conventional DCs (cDCs) from C3−/− and C5aR−/− mice are hyperresponsive to polyI:C, a TLR3 ligand, leading to enhanced NK‐cell activation. We found that cDCs lack C5a receptor (C5aR) and do not respond to C5a directly. Depletion of Gr‐1+ myeloid cells augments polyI:C‐induced cDC activation in WT but not in C3−/− or C5aR−/− mice, indicating that the effect of complement activation on cDCs is indirectly mediated through C5aR‐expressing Gr‐1+ myeloid cells. We further demonstrated that the mechanism by which Gr‐1+ myeloid cells regulate the activity of cDCs involves C5a‐dependent TGF‐β1 production in Gr‐1+ myeloid cells. C5a enhances and blocking C5aR decreases TGF‐β1 production in cultured bone marrow Gr‐1+CD11b+ cells. C5aR deficiency is associated with reduced circulating TGF‐β1 levels, while depleting Gr‐1+ myeloid cells abrogates this difference between WT and C5aR−/− mice. Lastly, we showed that enhanced cDC–NK‐cell activity in C3−/− mice led to delayed melanoma tumor growth. Thus, complement activation indirectly regulates cDC–NK‐cell activation in response to inflammatory stimuli such as TLR3 by promoting TGF‐β1 production in Gr‐1+ myeloid cells at steady state.