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Chicchi completed the route from San Jose in 4hr, 55min 2sec, with Juan Jose Haedo of Saxo-Bank second and stage-one winner Mark Cavendish of Columbia third in the same time.
Chicchi said the victory over elite sprinter Cavendish of Britain was especially sweet.
"Mark and I are rivals on the bike, but we are good friends off the bike," the 29-year-old Italian said. "Winning is always good, but to beat the number one is even better."
Seven-time Tour de France winner Lance Armstrong survived a scary moment when he was briefly caught up by a crash in the closing stages.
The incident came within three km of the finish, so he finished in the time of the main group and remained 27 seconds back.
"There was a short moment of fear when we saw that Lance was in the crash in the last lap," RadioShack team manager Johan Bruyneel said on the team's website. "Fortunately he didn’t crash himself. It was in the last 3km so there was no time loss."
Zabriskie, riding for Garmin-Transitions, retained the lead he took over with his stage three victory. He leads Australian Michael Rogers of Columbia by 4sec.
Three-time defending champion Levi Leipheimer of Armstrong's RadioShack team also finished in the main pack to remain third overall, six seconds behind Zabriskie.
Thursday's fifth stage takes riders 195.5 km from Visalia to Bakersfield,into the foothills of the Sierra Nevada Mountains. The race concludes Sunday.
