Leishmaniasis is a largely neglected infection caused by Leishmania spp. parasites. The first-line treatment, antimoniate meglumine, has a large number of adverse effects, high cost, and is developing resistance, hence the necessity of developing new alternatives. We report here the synthesis of (2E)-1-[1-(4-methoxyphenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-3-arylprop-2-en-1-one derivatives and the evaluation of their leishmanicidal activities. A series of 16 compounds were synthesized in three steps starting from p-anisidine with moderate to good yields and their biological activities were evaluated in vitro on Leishmania mexicana promastigotes and RAW 264.7 cells. The synthesis of the 1,2,3-triazol and chalcone moieties were made using a cycloaddition with acetylacetone followed by a Claisen-Schmidt condensation using different substituted benzaldehydes. Our results indicate that ten compounds were active against the parasite with IC₅₀ between 0.8-11.6 µM. Most of the active compounds are fluorinated, being the most active compound one that presents an o-trifluoromethyl moiety.