  The light of the first astrophysical objects is expected to leave an imprint
on the global 21-cm signal as it heats, excites, and ionizes neutral hydrogen.
This dependence on early astrophysics introduces significant uncertainties in
modeling the 21-cm signal during Cosmic Dawn (CD). Here we show that a
combination of observables including high-redshift UV luminosity functions, the
cosmic X-ray background, the optical depth to reionization, and hydrogen
absorption lines in quasar spectra, can be used to mitigate the astrophysical
uncertainties assuming minimal modeling. Beyond its implications to standard
astrophysics, we demonstrate how applying this procedure can improve
sensitivity to new physics signatures in the global 21-cm signal. Taking the
scenario of fractional millicharged dark matter (DM) as an example, we address
astrophysical systematics to produce interesting predictions for upcoming
experiments.
