The vulnerability for schizophrenia-spectrum disorders is expressed across a continuum of clinical and subclinical symptoms and impairment known as schizotypy. Schizotypy is a multidimensional construct with positive, negative, and disorganized dimensions. Openness to experience offers a useful personality domain for exploring multidimensional schizotypy. This study examined the factor structure of openness and its relation to schizotypy using the Multidimensional Schizotypy Scale-Brief (MSS-B) in a sample of 2,236 adults. Positive schizotypy was broadly associated with elevated openness and negative schizotypy was generally associated with diminished openness. Principal components analysis of 15 openness facets replicated the four-factor structure of openness including Fantasy/Feelings, Eccentricity, Nontraditionalism, and Ideas factors. All three schizotypy dimensions were associated with Eccentricity. Positive schizotypy was associated with Fantasy/Feelings, whereas negative schizotypy was inversely associated with Fantasy/Feelings. Results support the construct validity of the MSS-B, use of alternative openness measures in examining schizotypy, and the multidimensional structures of schizotypy and openness.