Following his seventh season with the Athletics, Zito signed a seven-year deal with the San Francisco Giants worth $126 million, plus $18 million option for 2014 with a $7 million buyout.
Zito's contract on December 29, 2006, became the highest for any pitcher in Major League history at the time.

During spring training in 2007, he and Barry Bonds made shirts that read "Don't ask me, ask Barry" with an arrow pointing to the other Barry.
By all accounts, Zito and Bonds got along well during their short time as teammates, and Zito made a point of saying he would stand by Bonds through onslaughts from the media.

In his first start as a member of the Giants, Opening Day (April 3), Zito went five innings and allowed two earned runs against the San Diego Padres.
He would take the loss.
In his next start, Zito struggled.
He went six innings but allowed eight earned runs against the Los Angeles Dodgers.
Zito would earn his first win as a member of the Giants in his next start on April 16 when he went six innings, gave up three hits, and allowed no runs to the Colorado Rockies. "
I've been trying to have a good game", Zito said. "
You can't try to do anything.
You either do or you don't.
I tried to get too fine with my pitches.
I wasn't aggressive."

On May 18, Zito made his return to Oakland as a Giant.
He lasted only four innings as he gave up seven runs while walking seven, including two bases-loaded walks.
The A's beat the Giants, 15–3.
He faced his old team again on June 9, this time in San Francisco.
Zito pitched four innings while giving up three earned runs on nine hits in a 6–0 defeat.

Zito made his first Major League relief appearance on August 5 against the Padres due to an early exit by starter Noah Lowry and an overworked bullpen.
He pitched a scoreless seventh inning.
He recorded his first career run batted in (RBI) two days later against the Nationals' Mike Bacsik, in the same game that Barry Bonds hit his record-breaking 756th career home run.

After Zito's start on August 12, his ERA was 5.13.
Over his final nine starts, he posted the fifth-best ERA in the NL, at 3.10.
He also had a 3–2 record.
He admitted that he had put pressure on himself to perform because of the large contract and was learning that he just needed to be himself.
Zito also said that it had been difficult for him to adjust to a new league, team, and ballpark.
On the final day of the season, in Los Angeles against the Dodgers, Zito allowed two runs on five hits and had four strikeouts in an 11–2 win.
For the first time in his career, Zito had a losing record, as he finished the season at 11–13.
He failed to reach 200 innings (​196 ²⁄₃) for the first time since 2000 and posted a career-high 4.53 ERA.
Following his seventh season with the Athletics, Zito signed a seven-year deal with the San Francisco Giants worth $126 million, plus $18 million option for 2014 with a $7 million buyout. Zito's contract on December 29, 2006, became the highest for any pitcher in Major League history at the time.
During spring training in 2007, he and Barry Bonds made shirts that read "Don't ask me, ask Barry" with an arrow pointing to the other Barry. By all accounts, Zito and Bonds got along well during their short time as teammates, and Zito made a point of saying he would stand by Bonds through onslaughts from the media.
In his first start as a member of the Giants, Opening Day (April 3), Zito went five innings and allowed two earned runs against the San Diego Padres. He would take the loss. In his next start, Zito struggled. He went six innings but allowed eight earned runs against the Los Angeles Dodgers. Zito would earn his first win as a member of the Giants in his next start on April 16 when he went six innings, gave up three hits, and allowed no runs to the Colorado Rockies. "I've been trying to have a good game", Zito said. "You can't try to do anything. You either do or you don't. I tried to get too fine with my pitches. I wasn't aggressive."
On May 18, Zito made his return to Oakland as a Giant. He lasted only four innings as he gave up seven runs while walking seven, including two bases-loaded walks. The A's beat the Giants, 15–3. He faced his old team again on June 9, this time in San Francisco. Zito pitched four innings while giving up three earned runs on nine hits in a 6–0 defeat.
Zito made his first Major League relief appearance on August 5 against the Padres due to an early exit by starter Noah Lowry and an overworked bullpen. He pitched a scoreless seventh inning. He recorded his first career run batted in (RBI) two days later against the Nationals' Mike Bacsik, in the same game that Barry Bonds hit his record-breaking 756th career home run.
After Zito's start on August 12, his ERA was 5.13. Over his final nine starts, he posted the fifth-best ERA in the NL, at 3.10. He also had a 3–2 record. He admitted that he had put pressure on himself to perform because of the large contract and was learning that he just needed to be himself. Zito also said that it had been difficult for him to adjust to a new league, team, and ballpark. On the final day of the season, in Los Angeles against the Dodgers, Zito allowed two runs on five hits and had four strikeouts in an 11–2 win. For the first time in his career, Zito had a losing record, as he finished the season at 11–13. He failed to reach 200 innings (​196 ²⁄₃) for the first time since 2000 and posted a career-high 4.53 ERA.
Barry Zito