Chronic progressive neuro-Behçet's disease (CPNBD) is characterized by slowly progressive cognitive decline, cerebellar ataxia, and brainstem atrophy without acute encephalomeningitis. To evaluate the progression of CPNBD during treatment, we conducted a retrospective, longitudinal comparative analysis of the clinical features and brain magnetic resonance imaging (MRI) in patients with CPNBD. We classified participants into three groups: NBD with acute encephalomeningitis alone (Group A, 8 patients with acute neuro-Behçet's disease [ANBD]), primary progressive CPNBD (Group B, 3 patients), and a combination of acute encephalomeningitis, and chronic progression (Group C, 2 patients). Routine laboratory tests and monthly rate of enlargement of the width of the third ventricle (ΔWTVm) and relative value of ΔWTVm to the transverse cerebral diameter (ΔWTVIm) were statistically evaluated. Although higher cell count values and interleukin-6 concentration in the cerebrospinal fluid were observed in ANBD, both ΔWTVm (p = 0.008) and ΔWTVIm (p = 0.008) were significantly larger in CPNBD phase than in the ANBD phase. Effective treatment for CPNBD seemed to reduce ΔWTVm and ΔWTVIm in some patients. Sequential evaluation of WTV in patients with CPNBD is a highly sensitive candidate biomarker of early diagnosis and treatment efficacy.