US 290 travels southeast to Ledbetter, where it then travels through additional grassland before bounding northeast to Burton. The highway then enters Brenham, where it briefly joins SH 36 to serve Blinn College and bypass the city as a four-lane freeway. After exiting Brenham, US 290 runs parallel to the old Washington County Railroad and goes through Chappell Hill to serve every historic landmark there, then crosses the Brazos River to move through a rural auto-industrial area. SH 6 joins US 290 north of Hempstead, where the two highways become a four-lane freeway notable for its role as a hurricane evacuation route. Running parallel to the Houston and Texas Central Railway from the north, US 290 finally comes right next to it roughly prior to intersecting SH 99. The highway is then designated as Northwest Freeway (legally as the Ronald Reagan Memorial Highway) as it travels through the suburb of Cypress, later splitting off SH 6 to the south in the suburb of Jersey Village. Following an interchange with the Sam Houston Tollway, US 290 serves several businesses and neighborhoods in northwest Houston before terminating at an interchange with I-610 west of the Lazybrook/Timbergrove district.