Multiple sclerosis (MS) is a clinically heterogeneous multifactorial disorder which is one of the most prevalent neurological disorders of females and young people. Both genetic and environmental factors are playing an important role in the pathophysiology of MS. The main objective of this study is to identify the relationship between numbers of genetic variants within different candidate genes (IL7R, LAG3, and CD40) and the risk of developing MS in the Jordanian Arab population. This case-control study consists of 218 MS patients chosen from neurology clinics at different hospitals in Jordan and ethnically matched 227 healthy controls. Genomic DNA was extracted from blood samples. Genotyping of the candidate gene polymorphisms was conducted using the Sequenom MassARRAY system. Statistical analysis was performed to identify the genetic association of the studied SNPs with MS. Twenty-one variants were studied, three of them were found to be associated with MS (rs6897932 (P-value=0.01) and rs13188960 (P-value=0.005) within IL7R gene and LAG3 rs2365095, (P-value=0.03) within LAG3 gene). Moreover, no significant association was found between MS and the genetic polymorphisms of the CD40 gene. After correction for multiple comparisons, only rs13188960 SNP remained significantly with MS. This is the first study of the genetic association with MS in the Jordanian Arab population to provided evidence of the genetic association of IL7R (rs6897932, rs13188960) and LAG3 (rs2365095) gene polymorphisms with MS. These findings may contribute to our understanding of MS and optimize the therapy protocol for individuals.