Beginning at M.J. Cuenco Avenue in the east, the boulevard heads northwest towards Fuente Osmeña circle and ends at Escario Street.
Osmeña Boulevard begins as a four-lane undivided road at the intersection with M.J. Cuenco Avenue near Plaza Independencia, San Roque area.
At Sanciangko Street just past the University of Cebu main campus, the boulevard divides slightly and becomes three lanes each way.
It intersects with Natalio Bacalso Avenue and traverses Santa Cruz and Sambag passing Cebu Normal University and Abellana National School.
Also in the vicinity of Natalio Bacalso and Pantaleon del Rosario Street are the University of San Carlos and Cebu City Sports Complex.