Zambrano shut out the Rockies on two hits, retiring the first 14 hitters before Matt Holliday got a two-out single in the fifth inning.
Only three Rockies lifted the ball over the infield as Zambrano registered 19 groundouts and five strikeouts while facing only two over the minimum.
The last Cubs pitcher to throw a no-hitter was Milt Pappas, who lost a perfect game with a two-out, two-strike walk in the ninth on Sept. 2, 1972.
With the wind blowing in at 15 m.p.h. and the Rockies running on fumes after getting into Chicago early Friday morning following a night game in Montreal, conditions were perfect for Zambrano's sinker.
"When I came out and saw the wind blowing in, I was happy," Zambrano said.
Zambrano (3-1) has allowed two or fewer earned runs in five of his six starts, posting a 2.18 earned-run average. He threw only 97 pitches in the second complete game of his career, trusting his fastball to carry him through most of the game.
"We all get older and wiser," Cubs manager Dusty Baker said. "That's what's happening with Carlos."
When Zambrano breezed through the first four innings without allowing a baserunner, the crowd of 37,307 began to sense something special. But when Holliday singled, Zambrano was brought back to earth.
"You can't think about that," Zambrano said. "You have to wait until the seventh or eighth inning before you realize you have a no-hitter. I really don't pay attention too much to the crowd. I like to be focused on what I'm doing."
"I had it in mind [Friday], the way he was throwing, that he could've done it," Barrett said.
Estes (4-2), the former Cubs starter, showed why he was not asked to return. The veteran left-hander allowed nine runs on seven hits, five walks and a hit batsman, while throwing 70 pitches in 22/3 innings. His earned-run average rose to 7.34.
The Cubs sent 11 men to the plate in the second, scoring six runs on three hits, four walks and the hit batter. After giving up three more in the third to make it 9-0, Estes received a standing ovation on his way to the dugout.
Much like his stay in Chicago, Estes was victimized by walks and singles rather than the long ball. The only ball hit really hard against him was Corey Patterson's three-run double in the second that center fielder Jeromy Burnitz nearly caught before crashing face-first into the doors near the 368-foot marker in left.
"It might have been a different story if Burnitz had made that sensational catch out there," Baker said. "It still would've been a real close game. It was a big play for [Burnitz] even getting to the ball."
Patterson had four RBIs and the Cubs have scored 11 runs in back-to-back games after averaging 2.3 runs per game in their previous nine.