The complementary reporter ion approaches overcome the ratio-compression problem of multiplexed proteomics and enhance the accuracy of protein quantification at the MS2 level. However, resolving the high m/z complementary ions encoded via mass defects in carbon and nitrogen (∼6.32 mDa mass difference in TMT/TMTpro) requires mass resolution and scan speeds above the performance levels offered by even the state-of-the-art Orbitrap™ instruments. Therefore, complement ion quantification (TMTc/TMTproC) is currently limited to only 5 (TMT) or 9 (TMTpro) channels (∼1 Da spaced) versus 11 or 18, respectively, when analyzing the conventional low m/z reporter ions. Here, we first demonstrate the feasibility of the highly-plexed complementary ion quantification in the high m/z range by enabling ultra-high-resolution (UHR) capabilities on a commercial Orbitrap mass spectrometer. The UHR performance required 3 s time-domain transients, which were acquired and processed with the high-performance data acquisition-processing system FTMS Booster X2 externally interfaced with the Orbitrap Fusion™ Lumos™ instrument. Despite validating the TMTc approach for the whole mass range, the UHR capability is incompatible with the practical data acquisition times (scan speeds) for liquid chromatography (LC)-based proteomics. We thus implemented a super-resolution mass spectrometry approach based on the least-squares fitting (LSF) that resolves even the 6.32 mDa doublets for all TMTproC channels in the whole mass range with time-domain transients as short as ∼108 ms (resolution setting of 50 000 at m/z 200). A more demanding, quantitatively accurate TMTproC performance is provided at the resolution setting of 120 000 at m/z 200 (256 ms time-domain transients). This advance enables accurate, LC timescale-compatible, and highly-multiplexed proteomics at the MS2 level.