It serves as the primary road through the Napa Valley, providing access to the Lake County region to the north and the rest of the San Francisco Bay Area to the south.

SR 29 continues as a 2-lane road through the Napa Valley cities of Oakville, Rutherford, St. Helena, and Calistoga, while also passing many of the region's notable vineyards and wineries.

This portion of the highway is often heavily congested with rental cars and tour buses in spring and summer, when tourists flock to Napa Valley.

[6] Historically, the route between the Napa Valley and Middletown was served by the Old Bull Trail Road, built by volunteers in the 1850s, that had grades of up to 35 percent.

Except where prefixed with a letter, postmiles were measured on the road as it was in 1964, based on the alignment that existed at the time, and do not necessarily reflect current mileage.