Objective of this study was to test whether there is a difference between chronic rhinosinusitis patients with (CRSwNP) and without (CRSsNP) nasal polyps in the association of extent of disease on CT scans with symptom severity and health-related quality-of-life (HRQL) impairment. Data sets from 271 chronic rhinosinusitis (CRS) patients who completed the Sino-Nasal Outcome Test 22 (SNOT-22) and visual analog scale (VAS) scores were subjected to principal component analysis (PCA) to identify a symptom components related to CRS. After controlling for demographics, medical therapy, and comorbidities, the association between symptom components/items excluded from PCA and Lund-Mackay score (LMS) was evaluated. No association was found between the total SNOT-22 score and LMS in CRS patients. There was an independent association between a higher "nasal" symptom component derived from SNOT-22 PCA and LMS in patients with CRSwNP (p < 0.001), but not in CRSsNP patients, with a statistically significant difference between two patient subsets (p = 0.003). In patients with CRSsNP, higher (worse) SNOT-22 "facial pain" was associated with lower LMS (p = 0.022), although the estimated change in LMS was modest. Considering VAS PCA components, higher "nasal" symptoms were associated with higher LMS in CRSwNP patients (p < 0.001) but not in CRSsNP, with a statistically significant difference between CRS groups (p = 0.024). A higher "pain" PCA component was associated with lower LMS in CRSsNP patients (p = 0.019). This study found significant differences in the relationship between symptom burden and CT scores between CRS phenotypes and no association between HRQL impairment and CT scores.