I-664 begins at a full Y interchange with I-64 and I-264 that serves as the terminus of all three Interstates in the Bowers Hill section of the city of Chesapeake. I-64 heads southeast as a continuation of the Hampton Roads Beltway through Chesapeake while I-264 heads east toward Portsmouth and Norfolk. I-664 heads west as an eight-lane freeway that has a southbound-only exit ramp to US 13 and US 460 (Military Highway) and crosses over Military Highway and a Norfolk Southern Railway rail line. The Interstate has a cloverleaf interchange with Military Highway, which here carries US 58 in addition to US 13 and US 460. The interchange also provides access to US 460 Alternate, which follows US 58 east into Portsmouth. I-664 curves north as a four-lane freeway that crosses Goose Creek and has a diamond interchange with SR 663 (Dock Landing Road) and a cloverleaf interchange with SR 337 (Portsmouth Boulevard).
Just south of its partial cloverleaf interchange with SR 659 (Pughsville Road), I-664 crosses a rail line; a spur from that rail line heads north in the median of the freeway as the highway enters the city of Suffolk. The rail spur leaves the median and heads northeast toward Portsmouth just south of its interchange with SR 164 (Western Freeway) and US 17 (Bridge Road). SR 164 heads east toward downtown Portsmouth while US 17 heads northwest to the James River Bridge. There is no access from southbound I-664 to southbound US 17; that movement is made via the next interchange, a cloverleaf interchange with SR 135 (College Drive) that serves satellite campuses of Tidewater Community College and Old Dominion University and the community of Churchland.
North of SR 135, northbound I-664 has a vehicle inspection station and crossovers before the highway enters the Monitor-Merrimac Memorial Bridge-Tunnel. The bridge-tunnel passes to the west of Craney Island, an artificial island in the city of Portsmouth that lies to the west of the mouth of the Elizabeth River. West of the highway is the confluence of the James River and Nansemond River to form Hampton Roads, as well as the James River Bridge a short distance to the north on the namesake river. I-664 heads north-northeast along a causeway for 3 miles (4.8 km) to a point west of the Newport News Middle Ground Light, where the pair of bridges curve to the north-northwest onto an artificial island where the highway descends into a pair of tunnels under the estuary's main shipping channel. The Interstate resurfaces on another artificial island at Newport News Point east of the coal piers in the city of Newport News.
I-664 has a southbound vehicle inspection station adjacent to its first interchange in Newport News, with Terminal Avenue. The Interstate parallels the southern end of CSX's Peninsula Subdivision as it passes through interchanges with several streets to the east of downtown Newport News. The southern interchange has ramps to and from 25th, 26th, and 27th streets; the first two streets carry eastbound and westbound US 60, which is unmarked from I-664. The northern interchange has ramps to and from 35th Street and Jefferson Avenue; Jefferson Avenue is SR 143, which is also unmarked from the Interstate. I-664 curves east as a six-lane freeway away from the railroad and has an oblique crossing of SR 351 (39th Street) prior to half-diamond interchanges with Roanoke Avenue and Chestnut Avenue. The Interstate enters the city of Hampton and has diamond interchanges with Aberdeen Road and Powhatan Parkway before reaching its northern terminus at I-64. I-664 meets its parent highway at a directional T interchange above Newmarket Creek just south of Hampton Coliseum. The Hampton Roads Beltway continues east along I-64 through Hampton before crossing Hampton Roads on the Hampton Roads Bridge-Tunnel into the city of Norfolk.