To evaluated artemisinin partial resistance (ART-R) in malaria in Burundi, during December 2023-June 2024, we studied 423 children <5 years of age with uncomplicated Plasmodium falciparum malaria in 8 health facilities in the northern part of the country. After artemether/lumefantrine treatment with only the first dose directly observed, 4.5% remained parasitemic on day 3. No pfkelch13 mutations, validated or candidate markers of ART-R, were detected. However, markers of antifolate and 4-aminoquinoline resistance were widespread: the dhfr triple mutant N51I/C59R/S108N was nearly fixed (92%), dhps double and triple mutants were common (41% and 47%), and pfcrt CVIET, associated with chloroquine and amodiaquine resistance, predominated (84%). Geographic differences occurred in day-3 positivity and haplotype frequencies. Although ART-R markers were absent, delayed parasite clearance and near fixation of multidrug-resistant haplotypes serve as a warning. Strengthened efficacy monitoring and regional molecular surveillance are urgently needed to prevent drug-resistant P. falciparum from becoming established in Burundi.