Most mortgages in the United States are securitized in agency mortgage-backed securities (MBS), and thus the yield spreads on these securities are a key determinant of homeowners’ funding costs. We study the variation in these spreads, over time and across securities, and document that they display a cross-sectional smile pattern with respect to the securities’ coupon rates. We propose non-interest-rate prepayment risk as a candidate driver of the spread variation and present a new pricing model that uses “stripped” MBS prices to identify the contribution of this risk. The pricing model finds the smile to be explained by prepayment risk, while the time-series variation is mostly accounted for by a non-prepayment risk factor that co-moves with MBS supply and credit risk in other fixed-income markets. We then study the MBS market’s response to the Fed’s large-scale asset purchases and use the pricing model to interpret the post-announcement divergence of spreads across MBS.