The major highway crossing through the Mojave Desert is Route 66.

Route 66, famously known as the "Main Street of America," runs through the heart of the Mojave Desert. Stretching from Chicago to Santa Monica, this iconic highway holds deep cultural and historical significance. The Mojave Desert portion of Route 66 offers travelers a glimpse of classic Americana, featuring vintage motels, diners, and roadside attractions. Despite being partially replaced by modern interstates, Route 66 remains a symbol of the American road trip, drawing tourists from around the world who seek to experience its timeless charm and vast desert landscapes.