Aiming to discover novel antifungal agents, a series of 2‑substituted‑4‑amino-quinolines and -quinazoline were prepared and characterized using IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and HRMS spectroscopic techniques. Their antifungal activities against four invasive fungi were evaluated, and the results revealed that some of the target compounds exhibited moderate to excellent inhibitory potencies. The most promising compounds III<sub>11</sub>, III<sub>14</sub>, III<sub>15,</sub> and III<sub>23</sub> exhibited potent and broad-spectrum antifungal activities with MIC values of 4-32 μg/mL. The mechanism studies showed that compound III<sub>11</sub> (N,2-di-p-tolylquinolin-4-amine hydrochloride) did not play antifungal potency by disrupting fungal membrane, which was quite different from many traditional membrane-active antifungal drugs. Meanwhile, III<sub>11</sub> also demonstrated a low likelihood of inducing resistance, and excellent stability in mouse plasma. In addition, some interesting structure-activity relationships (SARs) were also discussed. These results suggest that some 4‑aminoquinolines may serve as new and promising candidates for further antifungal drug discovery.