After 1.7 miles (2.7 km), it intersects Route 197 and turns northeast, crossing the river into Webster.

The route then crosses the Turnpike and passes the Auburn Mall, continuing alongside I-290 into Worcester.

Shortly after entering Worcester, Route 12 turns west as Hope Avenue, crossing I-290 at an incomplete interchange.

From the interchange it forms the southern and western boundaries of Hope Cemetery, as it turns north on Webster Street.

After passing the Worcester Polytechnic Institute and the American Antiquarian Society, the routes turn northward and intersect Grove Street.

Route 122A departs westward on Grove Street, while Route 12 continues north as a pair of wide one-way roads: Gold Star Boulevard northbound and West Boylston Street southbound.

The pair encounter an interchange with Interstate 190 next to the Greendale Mall, after which West Boylston Street carries both directions of Route 12, continuing north past Quinsigamond Community College.