Abstract <p>In this study, a series of novel pyrimidine derivatives incorporating an 1,1,2-trifluoro-1-butene moiety were synthesized and their structures were confirmed by ¹H NMR, ¹³C NMR, and HRMS. The bioassay results demonstrate that 4-methyl-2-[(3,4,4-trifluorobut-3-en-1-yl)thio]-6-(trifluoromethyl)pyrimidine exhibits comparable in vitro antifungal activity against <i>Aspergillus niger</i> (64.55 and 48.85%, respectively) at concentrations of 100 and 50 μg/mL when compared to Prochloraz. Additionally, 4-methyl-2-[(3,4,4-trifluorobut-3-en-1-yl)sulfonyl]-6-(trifluoromethyl)pyrimidine demonstrates superior nematocidal activity against <i>Caenorhabditis elegans</i> at concentrations of 100 and 50 μg/mL after 48 h with corrected mortality rates of 89.65 and 79.47%, respectively, surpassing those observed for ethoprophos. To the best of our knowledge, this study presents the first report on the synthesis and antifungal and nematocidal activities of novel pyrimidine derivatives incorporating an 1,1,2-trifluoro-1-butene moiety.</p>