Significance The HA glycoprotein enables viral entry into host cells and is the main target for antibodies in our immune system. While HA has now been established as a validated target for drug discovery, no FDA-approved small molecules are available that specifically prevent HA from binding host receptors or inhibit its membrane fusion activity and, thus, prevent infection. We, therefore, designed a fluorescence polarization probe to enable rapid identification of small molecules that bind to the stem fusion machinery of group 1 HAs. Application of our assay yielded a small molecule to the influenza A group 1 HA stem with antiviral efficacy.