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ABSTRACT We forecast the prospects for cross-correlating future line intensity mapping (LIM) surveys with the current and future Ly-α forest measurements. Using large cosmological hydrodynamic simulations, we model the emission from the CO rotational transition in the CO Mapping Array Project LIM experiment at the 5-yr benchmark and the Ly-α forest absorption signal for extended Baryon Acoustic Oscillations (BOSS), Dark energy survey instrument (DESI), and Prime Focus multiplex Spectroscopy survey (PFS). We show that CO × Ly-α forest significantly enhances the detection signal-to-noise ratio (S/N) of CO, with up to $$300{{\ \rm per\, cent}}$$ improvement when correlated with the PFS Ly-α forest survey and a 50–75 per cent enhancement with the available eBOSS or the upcoming DESI observations. This is competitive with even CO × spectroscopic galaxy surveys. Furthermore, our study suggests that the clustering of CO emission is tightly constrained by CO × Ly-α forest due to the increased sensitivity and the simplicity of Ly-α absorption modelling. Foreground contamination or systematics are expected not to be shared between LIM and Ly-α forest observations, providing an unbiased inference. Ly-α forest will aid in detecting the first LIM signals. We also estimate that [C ii] × Ly-α forest measurements from Experiment for Cryogenic Large-Aperture Intensity Mapping and DESI/eBOSS should have a larger S/N than planned [C ii] × quasar observations by about an order of magnitude.