Modern optical communication systems transmit multiple frequency channels, each operating very close to its theoretical limit. The total bandwidth can reach 10THz limited by the optical amplifiers. Maximizing spectral efficiency, the throughput per bandwidth is thus crucial. Replacing independent lasers with an optical frequency comb can enable very dense packing by overcoming relative drifts. However, to date, interference from non-ideal spectral shaping prevents exploiting the full potential of frequency combs. Here, we demonstrate comb-enabled multi-channel digital signal processing, which overcomes these limitations. Each channel is detected using an independent coherent receiver and processed at two samples-per-symbol. By accounting for the unique comb stability and exploiting aliasing in the design of the dynamic equalizer, we show that the optimal spectral shape changes, resulting in a higher signal to noise ratio that pushes the optimal symbol rate towards and even \emph{above} the channel spacing, resulting in the first example of frequency-domain super-Nyquist transmission with multi-channel detection for optical systems. The scheme is verified both in back-to-back configuration and in single span transmission of a 21 channel superchannel originating from a 25GHz-spaced frequency comb. By jointly processing 3 wavelength channels at a time, we achieve spectral efficiency beyond what is possible with independent channels. At the same time, one significantly relaxes the hardware requirements on digital-to-analog resolution and bandwidth, and well as filter tap numbers. Our results show that comb-enabled multi-channel processing can overcome the limitations of classical dense wavelength division multiplexing systems by enabling tighter spacing to reach the ultimate spectral efficiency in optical communications.