Cytoplasmic dynein 1 (dynein) is the primary minus end-directed motor protein in most eukaryotic cells. Dynein remains in an inactive conformation until the formation of a tripartite complex comprising dynein, its regulator dynactin and a cargo adaptor. How this process of dynein activation occurs is unclear, since it entails the formation of a three-protein complex inside the crowded environs of a cell. Here, we employed live-cell, single-molecule imaging to visualise and track fluorescently tagged dynein. First, we observed that only ~30% of dynein molecules that bound to the microtubule engaged in minus end-directed movement, and that too for a short duration of ~0.5 s. Next, using high-resolution imaging in live and fixed cells and using correlative light and electron microscopy and, we discovered that dynactin remained persistently attached to microtubules, and endosomal cargo remained in proximity to the microtubules and dynactin. Finally, we employed two-colour imaging to visualise cargo movement effected by single motor binding. Taken together, we discovered a search strategy that is facilitated by dynein’s frequent microtubule binding-unbinding kinetics: (1) in a futile event when dynein does not encounter cargo anchored in proximity to the microtubule, dynein unbinds and diffuses into the cytoplasm, (2) when dynein encounters cargo and dynactin upon microtubule-binding, it moves cargo in a short run. Several of these short runs are undertaken in succession for long-range directed movement. These discoveries were confirmed in a stochastic model incorporating dynamic motors binding to stationary cargo located along microtubules, and in a 3-state run-and-tumble particle (RTP) model that faithfully recapitulates the emergent cargo behaviour. In conclusion, we demonstrate that dynein activation and cargo capture are coupled in a step that relies on reduction of dimensionality to enable minus end-directed transport in cellulo.