With the game tied at 2 in the 10th against Trevor Rosenthal (0-1), Starlin Castro lined a single to right. Rizzo connected on an 0-1 pitch, launching it into the left-field bleachers for his seventh home run of the season. James Russell (5-0) picked up the win in relief.
"It's nice this early in his career to get his first walk-off in big-time fashion, and a home run, too," Cubs manager Dale Sveum said. "It was nice -- especially off a guy throwing 97, 98 mph -- to take that pitch opposite field and not try to do too much. It was awesome."
In 49 games last year with the Padres, Rizzo batted .141 with one home run. In 27 games since he was called up to the Cubs on June 26, he's hitting .333 with seven home runs. Sveum had heard that Rizzo had problems with fastballs. Not now.
"As soon as he got here, the lineup got deeper and got better," Cubs starter Paul Maholm said. "He's not up there just hacking. He's working the counts and goes the other way and just hitting what they give him. They tried to go away from him in the 10th, and [Rosenthal] got it up. He's come up with some huge hits."
Did the rookie take a deep breath in the 10th?
"Over my Minor League career and last year and this year, later innings, sometimes guys press a little harder, and I see veteran hitters relax at the plate and take pitches and not be too aggressive," Rizzo said. "That's something I took into this at-bat. I've always come up a little overanxious in situations like that, and I took a clean swing and let the rest take care of itself."
His plan: Keep it simple.
"Just hit the ball hard," Rizzo said of his approach. "I'm not really trying to move him over there. I'm trying to do some damage."
The runs were the first off Cardinals relievers in 19 2/3 innings.
"We can't be playing well and come in here and lose to the Cubs," St. Louis' Matt Holliday said. "We can't lose this series. But we did. The only way to get better is to play better. We didn't get the result we were looking for."
Rizzo got a hero's welcome at home plate, but Maholm deserved more than a no-decision. The Cubs starter held St. Louis to four hits over 6 2/3 innings. The Cardinals boast the best batting average against left-handed pitching in the Major Leagues, and had pummeled lefty Travis Wood on Friday, hitting five home runs in a 9-6 win.
St. Louis had two hits through six innings. In the seventh, David Freese singled with one out, reached third on Matt Carpenter's double and scored on Tyler Greene's sacrifice fly. Maholm walked pinch-hitter Lance Berkman, and Sveum met with the lefty and decided to stay with him against Daniel Descalso. But he walked to load the bases and Maholm was pulled. Manuel Corpas then got Allen Craig to fly out to right to end the inning.
This was Maholm's sixth consecutive start of at least six innings with one or no runs allowed, and he's the only Cubs left-hander to have such a streak since 1900. In Maholm's last six starts, he has given up five earned runs over 44 innings (1.02 ERA).
"Paulie is arguably the best pitcher the last month in all of baseball," Sveum said.
But instead of his 10th win, Maholm did not get a decision as Carlos Beltran ended an 0-for-13 skid when he tied the game at 2 with his 23rd home run with one out in the eighth off Shawn Camp.
Will Maholm still be on the Cubs after Tuesday's non-waiver Trade Deadline? Rizzo, Castro and Darwin Barney will be -- they're players the Cubs will build around. They need pitching, too.
"There was a reason I signed here," Maholm said. "I've always enjoyed playing here throughout my career. There's an option [for next year]. I finished last year hurt, and they gave me a chance to come in and prove I'm healthy, and I am. Hopefully, we can turn this into a long-term thing. We'll see how everything unfolds and go from there."
The Cubs are now 14-9 this month and have secured their first winning July since going 18-9 in 2009. Last year, they were 9-17 in July.
"Going into the second half, it was a goal to win a lot of baseball games and do whatever we could to get back to .500," Sveum said. "Obviously, it's an uphill battle to do it when we're  games under .500. Besides a pretty good hiccup against St. Louis [last weekend] against a really good offensive team, it's been a pretty good run of playing good baseball and winning a lot of games."