Background: The gene encoding a disintegrin and metalloproteinase domain 33 (ADAM33) is known to be associated with asthma in different ethnic groups. In Iraq, among the Arab ethnic background, this association has not yet been highlighted. Methods: One hundred and ninety-two asthmatics were examined; 118 males and 74 females (mean age 38.23 ± 9.13 years). The control group was 183; 110 males and the rest were females. The SNP of rs2280091 A/G (T1) was studied here to determine adam33 genotyping status using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The level of total IgE was measured using enzyme-linked immunosorbent assay (ELISA). Results: Significant differences (p = 0.004) in the frequencies of the ADAM33 mutant allele carriers between patients and controls were found OR = 1.62 (95% CI 1.16–2.27). This association was significant in individuals who carried homozygous (GG) or heterozygous (AG) variant type genotypes in a reference with carriers of wild- type (AA) genotypes. The odds ratios were 1.70 (95% CI 1.11–2.60, p = 0.013), 2.97 (95% CI 1.00–8.75, p = 0.047), 1.79 (95% CI 1.18–2.71 p = 0.005) for those who carried (wt/vt), (vt/vt), and (wt/vt + vt/vt), respectively. Correlation based on gender shows the presence of a significant association (p = 0.01a) for female mutant allele carriers OR = 1.96 (95% CI 1.15–3.36), but not in the case of male. Significant difference (p = 0.02) in the frequencies of mutant G allele carrier compared to wild A allele carrier was also found correlated in patients with severe asthma than moderate or mild asthma, OR = 1.78 (95% CI 1.10–2.89). Serum total IgE level in patients with GG genotype (219.37 ± 108.49) was significantly higher than in patients with AG and AA ge- notypes, respectively (193.22 ± 85.83), (157.11 ± 92.10), (P = 0.001). Conclusions: Carries of GG and AG alleles T1 ADAM33 polymorphism are at a high risk of developing functional susceptibility of asthma.