Background Hepatitis B virus DNA (HBV-DNA) assessment is recommended for diagnosing and monitoring chronic hepatitis B (CHB) patients. Quantitative hepatitis B surface antigen (qHBsAg) estimation adjunct to HBV-DNA is vital for assessing HBV chronicity and therapeutic prognosis. This study aimed to estimate the qHBsAg and compare its diagnostic performance with that of the HBV-DNA levels in CHB patients from Bangladesh. Methodology A total of 148 CHB patients were enrolled in this study. qHBsAg and hepatitis B e-antigen (HBeAg) were estimated using chemiluminescent and enzyme immunoassays, respectively, and HBV-DNA was quantified using real-time polymerase chain reaction. The parameters and diagnostic performances were analyzed by receiver operating characteristic (ROC) curve analysis. Results The overall levels (mean ± SD) of qHBsAg, HBV-DNA, and alanine aminotransferase (ALT) among the total population (n = 148) were 3.45 ± 0.80 log10 IU/mL, 4.40 ± 2.44 log10 IU/mL, and 86.17 ± 39.06 IU/L, respectively. Significant differences were observed in the levels of both qHBsAg (p = 0.004) and HBV-DNA (p < 0.0001) in cases with HBeAg positivity. qHBsAg levels showed a weak positive correlation with the levels of HBV-DNA and ALT in HBeAg-positive CHB patients, but no such relationship was observed in HBeAg-negative CHB patients. ROC curve analysis showed that the area under the curve for the qHBsAg level to distinguish high HBV-DNA levels (>5 log10 IU/mL) was 0.653 (p = 0.002), which indicated an acceptable diagnostic performance. The best cut-off of qHBsAg for predicting high HBV-DNA levels was 3.469 log10 IU/mL. Conclusions Our results indicated that qHBsAg might be a useful marker for monitoring HBV-DNA in CHB patients throughout treatment and follow-up.