The first observation of the decay B 0 → D 0 ¯ D 0 K + π − is reported using proton-proton collision data corresponding to an integrated luminosity of 4.7 fb − 1 collected by the LHCb experiment in 2011, 2012 and 2016. The measurement is performed in the full kinematically allowed range of the decay outside of the D * − region. The ratio of the branching fraction relative to that of the control channel B 0 → D * − D 0 K + is measured to be R = ( 14.2 ± 1.1 ± 1.0 ) % , where the first uncertainty is statistical and the second is systematic. The absolute branching fraction of B 0 → D 0 ¯ D 0 K + π − decays is thus determined to be B ( B 0 → D 0 ¯ D 0 K + π − ) = ( 3.50 ± 0.27 ± 0.26 ± 0.30 ) × 10 − 4 , where the third uncertainty is due to the branching fraction of the control channel. This decay mode is expected to provide insights to spectroscopy and the charm-loop contributions in rare semileptonic decays.