Cooper instability (CI) associated with superconductivity in the two-dimensional semi-Dirac semimetals is attentively studied in the presence of attractive Cooper-pairing interaction, which is the projection of an attractive fermion–fermion interaction. Performing the standard renormalization group analysis shows that the Cooper theorem is violated at zero chemical potential but instead CI can be generated only if the absolute strength of fermion–fermion coupling exceeds certain critical value and transfer momentum is restricted to a confined region, which is determined by the initial conditions. Rather, the Cooper theorem would be instantly restored once a finite chemical potential is introduced and thus a chemical potential-tuned phase transition is expected. Additionally, we briefly examine the effects of impurity scatterings on the CI at zero chemical potential, which in principle are harmful to CI although they can enhance the density of states of systems. Furthermore, the influence of competition between a finite chemical potential and impurities upon the CI is also simply investigated. These results are expected to provide instructive clues for exploring unconventional superconductors in the kinds of semimetals.