Within Onondaga, NY 173 passes through both open areas with sparse development and areas containing built-up residential neighborhoods. The route heads southeast to Onondaga Hill, a large community built up just east of Onondaga Community College. Here, it overlaps with NY 175 for about before NY 175 forks off to the northeast into Syracuse. NY 173 continues eastward as the Seneca Turnpike, passing to the south of Community General Hospital before it enters the southernmost portion of Syracuse. This portion of the city is mostly residential, save for a smattering of businesses around NY 173's junctions with NY 80 and US 11. Near the midpoint of the route's stay in Syracuse, it crosses over Onondaga Creek, on the banks of which lie Faith Heritage School and Meachem Field. The route leaves the city limits shortly after passing under both directions of I-81.