Highway 87 runs north and south, beginning near the Gulf Coast in Port Lavaca, Texas providing access into New Mexico, and runs along the eastern side of Lamesa and is also known as Lynn Avenue. This highway provides access to many major intersections throughout the state of Texas.

U.S. Route 180 is an east to west U.S. Highway, terminating at Interstate 10 and Interstate 20. This highway travels in the center of Lamesa and is also known as North 4th Street. U.S. 180 will take you to many areas of Texas and travels through New Mexico and Arizona.

State Highway 137 is a north and south highway that extends from Ozona, Texas to Brownfield, Texas, traveling along Lamesa's western boundaries. This highway crosses a total of seven counties, providing connection to many intrastate and interstate thoroughfares.