The aim of this paper is to show that the spontaneous sliding of drops forming from an interfacial instability on the surface of a wall-bounded fluid film is caused by a symmetry-breaking secondary instability. As an example, we consider a water film suspended from a ceiling that drains into drops due to the Rayleigh–Taylor instability. Loss of symmetry is observed after the film has attained a quasi-steady state, following the buckling of the thin residual film separating two drops, whereby two extremely thin secondary troughs are generated. Instability emanates from these secondary troughs, which are very sensitive to surface curvature perturbations because drainage there is dominated by capillary pressure gradients. We have performed two types of linear stability analysis. Firstly, applying the frozen-time approximation to the quasi-steady base state and assuming exponential temporal growth, we have identified a single, asymmetric, unstable eigenmode, constituting a concerted sliding motion of the large drops and secondary troughs. Secondly, applying transient stability analysis to the time-dependent base state, we have found that the latter is unstable at all times after the residual film has buckled, and that localized pulses at the secondary troughs are most effective in triggering the aforementioned sliding eigenmode. The onset of sliding is controlled by the level of ambient noise, but, in the range studied, always occurs in the quasi-steady regime of the base state. The sliding instability is also observed in a very thin gas film underneath a liquid layer, which we have checked for physical properties encountered underneath Leidenfrost drops. In contrast, adding Marangoni stresses to the problem substantially modifies the draining mechanism and can suppress the sliding instability.