Malaria due to Plasmodium falciparum remains one of the most infectious diseases in the world. Resistance to most available antimalarial drugs has been the major challenge in managing the disease. There is therefore the need for novel antimalarial drugs to circumvent the current drug resistance and pre-empt future resistance. Another option is the reintroduction of previously abandoned antimalarial drugs to which the parasites have regain sensitivity as a result of reduced drug pressure. This susceptibility can be assessed by evaluating the polymorphic levels of the concerned biomarkers of drug resistance. Monitoring these biomarkers of drug resistance may be informative on the drug action. This study was aimed at assessing the polymorphic levels of Plasmodium falciparum Pfcrt (K76T) and pfmdr 1(N86Y) drug resistance markers in Buea, South West Region, Cameroon. Consented participants were recruited into the study and their socio-demographic data were collected using well-structured questionnaires. About 1mL of venous blood was collected by venipuncture from each of a total of 155 participants for parasitemia assessment by light microscopy and genetic analysis by PCR and RFLP. Parasite genomic DNA was extracted from the field isolates by the Chelex-PBS method. Single nucleotide polymorphism (SNP) genotyping was then undertaken by nested polymerase chain reaction (PCR) followed by allele-specific restriction analysis (ASRA). Results showed that 56.1 % (87) of the participants were afebrile. Parasitemia was independent (p>0.05) of sex and age. Febrile individuals had higher parasitemia than afebrile individuals. Plasmodium genomic DNA was successfully extracted from all the 155 samples and upon analysis, 153 (98.7%) were positive for P. falciparum mono infection and 2(1.3%) positive for Plasmodium ovale. Plasmodium malariae and P. vivax were not found. The prevalence of sensitive K76 and N86, were 37.3% and 55.6% respectively in the study area. This study shows a gradual return of the chloroquine sensitive genotypes due to the withdrawal of chloroquine from the treatment policies in Cameroon. However, the prevalence of wild type genotype is still lower than World Health Organization recommendation (≥ 90%) for a possible re-introduction in the treatment policy.