A series of novel indazole-pyrone hybrids were synthesized by a one pot reaction between <i>N</i>-alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2<i>H</i>-pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were obtained in good to excellent yields (72-92%) and characterized by NMR and single crystal X-ray diffraction. Nineteen compounds were tested <i>in vitro</i> against both <i>Leishmania donovani</i> (MHOM/ET/67/HU3, also called LV9) axenic and intramacrophage amastigotes. Among all, five compounds showed anti-leishmanial activity against intracellular <i>L. donovani</i> with an IC<sub>50</sub> in the range of 2.25 to 62.56 μM. 3-(1-(3-Chloro-2-ethyl-2<i>H</i>-indazol-6-ylamino)ethylidene)-6-methyl-3<i>H</i>-pyran-2,4-dione <b>6f</b> was found to be the most active compound for axenic amastigotes and intramacrophage amastigotes of <i>L. donovani</i> with IC<sub>50</sub> values of 2.48 ± 1.02 μM and 2.25 ± 1.89 μM, respectively. However, the cytotoxicity of the most promising compound justifies further pharmacomodulations.