At the western end of the river, I-295 continues west, serving as the border between Clay and Duval counties running just north of the town of Orange Park with interchanges at US Route 17 (US 17)/SR 15 (Roosevelt Boulevard) and SR 21 (Blanding Boulevard), serving NASJAX and Clay County.

Before turning north through the Westside of Duval County, the freeway also has a full interchange at east–west connector Collins Road to serve the Argyle and Oak Leaf areas in addition to NASJAX.

[3] The northern part of the I-295 loop, from Commonwealth Avenue just north of I-10 in the west to Town Center Parkway just north of J. Turner Butler Boulevard (SR 202) in the east consists of two general purpose lanes in each direction (with the exception of the Dames Point bridge which contains three lanes in each direction).

The I-295 East Beltway (formerly signed as SR 9A) was designated the Ronald Reagan Memorial Highway in an FDOT ceremony on August 27, 2009.

[5] In February 2011, construction began for a new interchange at Collins Road, just west of the congested Blanding Boulevard exit.

Extending from the southeast corner of the loop is I-795, currently signed as SR 9B, an approximately 5.5-mile (8.9 km) expressway connecting to I-95 and proceeding southward into St. Johns County.

[11] At least one motorist, William Klinedinst, died after a concrete block landed on the hood of his moving car, causing it to crash; his body was not identified for several weeks.

[12] The incidents spurred Governor Lawton Chiles to dispatch the Florida National Guard to patrol the roadway and the American Automobile Association (AAA) to issue a rare travel warning for the Interstate and direct its customers to avoid its use.

[11] A taskforce was set up by the Jacksonville Sheriff's Office to investigate the incidents, and, though charges were filed, they were eventually dropped.

[12] As of 2022[update], FDOT is conducting a study on widening the section between the Dames Point Bridge and J. Turner Butler Boulevard (SR 202).