Lakai Kirk was killed in the crash, which occurred around 3:30 p.m. on state Highway 121 south of Duhig Road near Napa.
The crash also injured Napa County restaurateur Cynthia Pawlcyn, 58, and her husband John Watanabe, 66, of St. Helena.
Flavio Castellanos, 23, of Napa, was in a 2011 Chevrolet Equinox driving north on Highway 121 when he crossed into the southbound lane at a curved part of the road and collided head-on with a 2012 Lexus RX450, CHP Officer Jaret Paulson said.
Castellanos suffered major injuries and was taken to the Queen of the Valley Hospital in Napa, Paulson said.
The 4-year-old boy, a passenger in the Chevrolet, was given first aid at the scene and was flown by the Sonoma County sheriff's helicopter to Queen of the Valley Hospital, where he was pronounced dead, Paulson said.
When the crash occurred, the boy was secured in a booster seat and the lap and shoulder restraints were in use, Paulson said.
Lakai's 25-year-old mother Ariel Kirk suffered major injuries in the collision and was taken to Santa Rosa Memorial Hospital.
In the Lexus, Pawlcyn suffered moderate injuries and Watanabe suffered minor injuries and both were taken to Queen of the Valley Hospital, Paulson said.
Pawlcyn owns Mustard's Grill in Napa and Cindy's Backstreet Kitchen in St. Helena and a catering business. She also has written cookbooks including "Grub Street San Francisco" and "Cindy's Supper Club: Meals From Around the World to Share With Family and Friends."
The crash closed Highway 121 for three hours.