Existing data suggest that people with multiple sclerosis (pwMS) are at an elevated risk for experiencing olfactory impairment. We investigated if smell dysfunction can be used as an MS disease marker. This is a cross-sectional, case−control study. All data were collected prospectively from 171 participants, 115 pwMS and 56 controls (age and sex stratified and matched to the patients), who reported smell, taste, and nasal breathing, and completed the Greek-validated questionnaires for nasal obstruction (NOSE), nasal-symptoms QoL (SNOT-22), and olfaction-associated QoL (QOD). The smell was assessed with the “Sniffin’ sticks” (odor threshold (OT), discrimination (OD), identification (OI) test, and total TDI). We recorded the pwMS disease characteristics (Expanded Disability Status Scale-EDSS, the disease type and duration), cognitive function, emotional status, fatigue, and impact of MS in everyday activities. A TDI < 30.75 (hyposmia) was detected in 30.8% of the patients. The patients’ OD and TDI scores were significantly lower than the controls’ (p = 0.005, and 0.015, respectively). The hyposmia correlated with disease severity and duration. The EDSS score correlated negatively with OD (r = −0.299, p = 0.001) and TDI (r = −0.242, p = 0.01). The disease duration correlated negatively with OD (r = −0.305, p = 0.001, OI (r = −0.253, p = 0.008) and TDI (r = −0.3, p = 0.001). The information processing speed (SDMT) correlated with OD, OT, and TDI (r = 0.302, p = 0.002; r = 0.242, p = 0.016; r = 0.326, p = 0.001). The olfactory function is changing in MS in accordance with disease progression.