<p>The dynamics of many nanoscale biological and synthetic systems such as enzymes and molecular motors are activated by thermal noise, and driven out-of-equilibrium by local energy dissipation. Because the energies dissipated in these systems are comparable to the thermal energy, one would generally expect their dynamics to be highly stochastic. Here, by studying a thermodynamically-consistent model of two coupled noise-activated oscillators, we show that this is not always the case. Thanks to a novel phenomenon that we term topological phase locking (TPL), the coupled dynamics become quasi-deterministic, resulting in a greatly enhanced average speed of the oscillators. TPL is characterized by the emergence of a band of periodic orbits that form a torus knot in phase space, along which the two oscillators advance in rational multiples of each other. The effectively conservative dynamics along this band coexists with the basin of attraction of the dissipative fixed point. We further show that TPL arises as a result of a complex, infinite hierarchy of global bifurcations. Our results have implications for understanding the dynamics of a wide range of systems, from biological enzymes and molecular motors to engineered nanoscale electronic, optical, or mechanical oscillators.</p>