The World Health Organization (WHO) estimates that over 300 million new cases of malaria occur yearly, with approximately two to three million deaths. Africa has 90% of the global burden with pregnant women and children being the most affected. Drug resistance has been identified as the major problem militating against global malaria control programs. This study was set out to access the prevalence of resistance to Chloroquine and Sulphadoxine/Pyrimethamine among children below the age of 5 years from Sagamu by identifying the molecular markers of resistance to Chloroquine and Sulphadoxine/Pyrimethamine after 6 years of change in National antimalarial policy in favor of Artesunate combination therapy (ACT). One hundred and thirty one children between the ages of 2 to 60 months were recruited for the study. Questioners were administered to the parents/guardian of the children to find out about their knowledge and use of insecticide treated net (ITN), chloroquine, Sulphadoxine/Pyrimethamine and ACT. Blood samples were also collected from participants to check for parasite density and molecular markers of resistance to both chloroquine and Sulphadoxine/Pyrimethamine. High rate of self medication with Chloroquine and Sulphadoxine/Pyrimethamine was observed in this study, the rate of use was 35.1% and 66.4% respectively while only 20.6% used the currently recommended ACT. Participants have a good knowledge of Insecticide treated net (96.9%) but the use of this modern malaria control measure was very low (19.1%). There is still a high selection pressure which was confirmed by the vi high prevalence of SP and Chloroquine resistance genes observed among all patients irrespective of frequency of use of both Chloroquine and Sulphadoxine/Pyrimethamine. The prevalence of Pyrimethamine resistance genes S108N, C59R, N51I and the S108N/C59R/N51I triple mutation was 88.2%, 76.5%, 64.7% and 56.3% respectively while there was a 98.3% prevalence of Chloroquine resistant genes. The implication of this is that as long as a significant number of Nigerians continue to use Chloroquine and Sulphadoxine/Pyrimethamine the selection pressure will continue to promote the circulation of resistant genes. This will defeat the purpose of the National strategy to rest these drugs so as to reduce the selection pressure and thereby reduce resistance, so that these drugs can be reintroduced in the future It is therefore recommended that there is more advocacy and public enlightenment to enlist the support of the public and also reduce the cost of Artesunate based combination therapies which are about 10-20 times more expensive than chloroquine-based therapies and prophylaxis by Sulphadoxine/pyremethamine.