We present the discovery of a powerful candidate microquasar in NGC 300, associated with the S 10 optical nebula (previously classified as a supernova remnant). Chandra images show four discrete X-ray knots aligned in the plane of the sky over a length of ≈150 pc. The X-ray emission from the knots is well fitted with a thermal plasma model at a temperature of ≈0.6 keV and a combined 0.3–8 keV luminosity of ≈10^37 erg s^−1. The X-ray core, if present at all, does not stand out above the thermal emission of the knots: this suggests that the accreting compact object is either currently in a dim state or occulted from our view. We interpret the emission from the knots as the result of shocks from the interaction of a jet with the interstellar medium (possibly over different epochs of enhanced activity). Cooler shock-heated gas is likely the origin also of the optical bubble and lobes near the X-ray structure, detected in images from the Hubble Space Telescope and the Very Large Telescope. In the radio bands, we observed the region with the Australia Telescope Compact Array, and discovered an elongated radio nebula (about 170 × 55 pc in size) with its major axis aligned with the chain of Chandra sources. The radio nebula has an integrated 5.5 GHz radio luminosity of |${\approx }10^{34}\, \rm{erg\,s^{-1}}$| for a distance of 1.88 Mpc. The morphology, size, and luminosity of the extended X-ray, optical, and radio structure suggest that NGC 300-S 10 belongs to the same class of powerful (P_jet > 10^39 erg s^−1) microquasars as SS 433, Ho II X-1, and NGC 7793-S 26.