Once south of U.S. 50, Stringfellow Road serves as the ZIP Code border between Chantilly (20151) and Fairfax (22033).

Westbound traffic can exit onto Stringfellow Road at all other times, but the exit is restricted to HOV-2+ traffic weekdays from 3:00 to 7:00 p.m.[1] South of the I-66 interchange, Stringfellow Road heads to an intersection with U.S. Route 29 (Lee Highway) at the Fairfax/Centreville/Clifton border.

After crossing SR 620 Clifton Road reduces from four to two lanes, although the speed limit remains 45 MPH.

During that approach the speed limit is gradually reduced to 25 MPH before intersecting with Newman Road.

Infrequently SR 645 is impassable due to flooding from Pope's Head Creek.

It then intersects with SR 643 / SR 612 (Henderson Road) which draws heavy traffic because it leads to the only crossing between Fairfax County and Prince William County that is not physically located at or near Woodbridge or Manassas.

It intersects with SR 643 (that road is called Burke Centre Parkway to the west, and Lee Chapel Rd.

(this is a split intersection because it is near the bridge over the Southern Railway tracks) where the speed limit decreases to 35 MPH.

It passes by Lake Braddock Secondary School and then leaves Burke when it intersects with SR 638 (Rolling Road), and crosses into Springfield.