The Colorado Rockies have dropped eight straight games at AT&T Park.
The odds seem to be in favor of Zito and the Giants completing a three-game sweep Wednesday, especially since Jeff Francis badly lost all three outings to the World Series champions a year ago.
San Francisco (5-3) is enjoying its longest run at home over Colorado (5-3) since winning nine in a row from 2003-04.
Zito (1-0, 0.00 ERA) figures to give the Giants a good chance to continue that streak. He's 5-0 with a 2.71 ERA in his last 11 versus the Rockies, and 10-0 with a 3.18 ERA in his last 15 overall.
The left-hander has limited Troy Tulowitzki to a .146 average while Dexter Fowler (.235) and Michael Cuddyer (1 for 11) have also fared poorly. Carlos Gonzalez is one of the few Rockies to enjoy success against Zito with a .296 mark while Todd Helton is batting .185 although his 10 walks give him a .405 on-base percentage.
Zito yielded three hits over seven innings Friday in a 1-0 home victory over St. Louis.
"He has a great game plan going into every game," catcher Buster Posey told the Giants' official website. "He's pitching with a lot of conviction, and I think one of the reasons he's doing that is he's so well-prepared."
Zito added a hit in his lone official at-bat against the Cardinals, but that will be hard to duplicate since he's 0 for 7 against Francis (1-0, 1.50).
Francis is 0 for 5 against Zito, but the Rockies southpaw is no doubt more concerned about whether he can improve against Giants sluggers Posey and Pablo Sandoval. Posey, who got the day off in Tuesday's 9-6 victory, is 5 for 8 with a homer against Francis while Sandoval is 4 for 9 with three doubles.
Hunter Pence, 9 for 27 during a seven-game hitting streak, is 3 for 17 against Francis.
Francis has lost his last four starts to the Giants, going 0-3 with a 10.03 ERA in three last year.
He pitched well Friday, giving up one run over six innings in a 5-2 victory over San Diego in the Rockies' home opener. Francis retired 14 of his last 15 batters.
"I just felt like I could throw anything," he said.
Brandon Crawford hit a three-run homer Tuesday and Pence had a pair of RBI singles for the Giants, who rallied from a 5-1 deficit in the second inning. Angel Pagan and Marco Scutaro had three hits apiece.
The Rockies had just two hits after their five-run second inning. One of them was Tulowitzki's solo homer in the fifth.
"The Giants just keep coming,'' Rockies manager Walt Weiss said. ''They won a championship playing like that. They string together a lot of good at-bats, there are a lot of tough outs over there. We couldn't shut them down.''
San Francisco pitchers have yielded three homers, with only Minnesota allowing fewer (two).