Chicago has won both games in the first series between the teams since the 1918 World Series.
"They know what I can do and I'm not really overanxious to beat them and do more than I can," said Walker, who spent the 2003 season with the Red Sox.
"It's nice to do well and win. I have to bite my tongue in certain situations because you don't what to give up too much information in a casual conversation. You might say something and (Jason) Varitek) will go, `All right' and go back and use it."
So far, the Red Sox haven't figured out a way to stop the Cubs, who had 20 hits in Friday's opener and collected 12 more Saturday.
"We talk about being just good enough to win. I agree that right now we're just good enough to lose and that's not good," Red Sox manager Terry Francona said. "Consistency at this level is so big and we're having a heck of a time finding it."
Walker singled off Wade Miller (2-2) in the sixth inning for his third hit, raced to third on Hollandsworth's double past third and scored on Blanco's sacrifice fly for a 5-4 lead.
Hollandsworth added an RBI single in the eighth and finished with three RBI.
Todd Wellemeyer (2-1) pitched one inning for the win. He replaced Zambrano, who left suddenly after warming up to start the sixth because of a sprained left big toe.
Zambrano, who made an awkward slide into second in the bottom of the fifth, walked off the mound after warming up and then off the field, accompanied by a trainer.
X-rays were negative and Zambrano should be ready for his next start, trainer Mark O'Neal said.
"He was looking back and lost sight of where the base was, so it was an ugly slide," Cubs manager Dusty Baker said. "It could have been a lot worse than that. We were hoping he could give us another inning, but he couldn't push off on that toe."
Zambrano departed with the game tied at 4 after the Red Sox had jumped to an early 4-0 lead on homers by Nixon and Bill Mueller.
The homer brought a large and loud Red Sox fan contingent to its feet at Wrigley Field. Cheers of "Let's go Red Sox!" could be heard throughout the game before they were overwhelmed by boos.
"Fans are into it. Quite frankly I wish we had this excitement almost every day because it picks us up," Baker said.
Zambrano, who had not given up an earned run in his two previous starts over 15 innings, allowed five hits and four runs in his five innings with eight strikeouts, throwing 98 pitches on a humid 84-degree day.
Miller gave up nine hits and five runs in seven innings. He was 4-0 in five previous starts at Wrigley Field with the Astros, including a two-hitter on May 30, 2003.
But with a 4-0 lead, he gave up five straight singles to open the bottom of the second.
"A couple of hits came off of decent pitches. They were able to get wood on it," Miller said.
"It's frustrating. I'm not pleased. I was able to settle down, but the damage was done after that inning."
Jeromy Burnitz, Aramis Ramirez, Walker, Hollandsworth and Blanco singled in succession to cut the Boston lead to 4-2. Zambrano then hit into a double play with the bases loaded as the third run scored.
"We got ourselves right back in the game without the long ball. We strung together a bunch of base hits and first-and-thirds," Hollandsworth said.
Chicago tied it in the fourth when Walker's liner into the right field corner went off Nixon's glove for a triple. After fouling a ball off his leg, Hollandsworth followed with an RBI grounder that was hit soft enough to score Walker, even with Boston's infield playing in.
Burnitz went to the ivy in right field to catch Mark Bellhorn's long drive in the eighth with the tying run on second.
- Miller had singles in his first two at-bats and became the first Boston pitcher to have a multihit game since Sonny Siebert did it against the Yankees in 1972.
- Cubs pitcher Kerry Wood, on the DL with sore shoulder, is slated to start a rehab assignment at Triple-A Iowa on Monday.
- The Cubs have won 12 of their last 16.
- Announced attendance was 39,096.