A new approach to optical fiber sensing is proposed and demonstrated that allows for specific measurement even in the presence of strong noise from undesired environmental perturbations. A deep neural network model is trained to statistically learn the relation of the complex optical interference output from a multimode optical fiber (MMF) with respect to a measurand of interest while discriminating the noise. This technique negates the need to carefully shield against, or compensate for, undesired perturbations, as is often the case for traditional optical fiber sensors. This is achieved entirely in software without any fiber postprocessing fabrication steps or specific packaging required, such as fiber Bragg gratings or specialized coatings. The technique is highly generalizable, whereby the model can be trained to identify any measurand of interest within any noisy environment provided the measurand affects the optical path length of the MMF’s guided modes. We demonstrate the approach using a sapphire crystal optical fiber for temperature sensing under strong noise induced by mechanical vibrations, showing the power of the technique not only to extract sensing information buried in strong noise but to also enable sensing using traditionally challenging exotic materials.