Cortical lesions (CL) and cortical atrophy are frequent in multiple sclerosis (MS) and main determinants of disease progression. The relationship between them is still unknown, mostly due to the low sensitivity of clinical magnetic resonance imaging (MRI) to CL. Disconnection from white matter (WM) lesions has also been proposed as a pathogenic mechanism for cortical MS atrophy. Using 7 Tesla MRI that has shown increased sensitivity to CL than clinical MRI, we showed, in a large MS cohort that WM lesions are the main determinant of cortical thinning. Nevertheless, CL resulted as the main contributors of physical and cognitive disability.