It then crosses the Connecticut River at the Calvin Coolidge Bridge, just downstream from Elwell Island.

Once in Worcester, Route 9 becomes a major thoroughfare through the city, as Park Avenue, Highland Street (which passes Major Taylor Boulevard), before passing over Interstate 290 and Belmont Street, where University of Massachusetts Medical School and the former Worcester State Hospital are located.

It enters the city of Boston by crossing over Brookline's former namesake, the Muddy River, part of the Emerald Necklace.

Route 9 loses its raised median briefly between its intersection with South Huntington Avenue and Brigham Circle.

This stretch is also a major site of baseball history; the first game of the 1903 World Series, baseball's first true World Series, was played at the Huntington Avenue Grounds, the original home of the Boston Red Sox.

The E branch of the MBTA Green Line roughly follows Huntington Avenue underground from Copley Square until it rises above ground at the Northeastern portal.

The Green Line E Branch then operates in a dedicated median of Huntington Avenue between Northeastern University and the Brigham Circle stop, where trains begin street running in mixed traffic to a terminus at Heath Street.

It then passes Copley Place and the Prudential Center complex, before splitting, the eastbound half onto Stuart Street, the westbound onto Saint James Avenue, past Copley Square; both the eastbound and westbound segments of Route 9 end at Route 28.

Further west, in Framingham, Route 9 was home to one of the first modern shopping malls, the aptly named Shoppers' World.