Interstate 5: This is the main north-south route that connects California with Oregon and Washington. It runs through San Joaquin County and provides access to Stockton, Lodi, Manteca, Tracy, and other cities. It also connects with other major highways such as I-580, I-205, I-80, and State Route 99.

State Route 99: This is another north-south route that parallels I-5 and serves the agricultural and urban areas of the San Joaquin Valley. It runs through Merced County and Stanislaus County and provides access to Merced, Modesto, Turlock, Ceres, and other cities. It also connects with other major highways such as SR-152, SR-120, SR-108/49, SR-4, SR-12/88/104/49.

State Route 120: This is an east-west route that connects the San Joaquin Valley with Yosemite National Park. It runs through Stanislaus County and Tuolumne County and provides access to Oakdale, Escalon, Manteca (via SR-99), Groveland (via SR-108/49), Yosemite Valley (via Big Oak Flat Road), Tioga Pass (via Tioga Road), and Mono Lake (via US-395).

State Route 108/49 (SR-108/49): This is a combined route that connects the San Joaquin Valley with the Central Sierra. It runs through Stanislaus County and Tuolumne County and provides access to Modesto (via SR-99), Riverbank (via SR-219), Oakdale (via SR-120), Jamestown (via SR-108), Sonora (via SR-49), Twain Harte (via SR-108), Pinecrest Lake (via SR-108), Sonora Pass (via SR-108), Bridgeport (via US-395), Angels Camp (via SR-49), San Andreas (via SR-49), Jackson (via SR-49), Sutter Creek (via SR-49), Amador City (via SR-49), Plymouth (via SR-49), El Dorado Hills (via US-50).

State Route 4: This is an east-west route that connects the San Francisco Bay Area with the Central Sierra. It runs through Calaveras County and Alpine County and provides access to Antioch (via I-680), Brentwood (via Vasco Road), Stockton (via I-5 or SR-99), Farmington (via Jack Tone Road), Copperopolis (via O’Byrnes Ferry Road), Angels Camp (via SR-49), Murphys (via Main Street or Big Trees Road), Arnold (via Blagen Road or Moran Road), Bear Valley Ski Resort (via Bear Valley Road or Ebbetts Pass National Scenic Byway), Markleeville (via Ebbetts Pass National Scenic Byway or Monitor Pass).