In this communication, we present the results of the five-fold differential cross-section (5DCS) and triple differential cross-section (TDCS) for the (e, 2e) process on molecular hydrogen (H2) by the plane wave and the twisted electron beam impact. The formalism is developed within the first Born approximation using the plane wave and the twisted wave for the incident electron beam. We describe the plane wave, Heitler–London type wave function, Coulomb wave for the scattered electron, the H2 molecular state, and the ejected electron. We compare the angular profiles of the 5DCS and TDCS for the different values of orbital angular momentum (OAM) number m of the twisted electron beam with that of the plane wave beam. We also present the 5DCS for different molecular orientations and study the effect of m on the 5DCS. We further investigate the influence of the twisted electron beam on the (e,2e) process on the H2 molecule from the perspective of the ‘Young-type’ interference of the scattered waves, emanating from the two atomic centers of the H2 molecule. We also study the TDCS for macroscopic H2 target to explore the effect of opening angle (θ
p) of the twisted electron beam on the TDCS. Our results clearly show the effect of the twisted electron’s OAM number (m) and the opening angle (θ
p) on the 5DCS and TDCS of the molecular hydrogen.