Rizzo homered off of Zack Wheeler to open the game in his first career plate appearance hitting leadoff.
"Saw the first pitch really well, just swung on the second pitch, it was right there," Rizzo said after the Cubs' 14-3 win. "Just wanted to stay through it and not try to do too much."
Cubs manager Joe Maddon finally acquiesced to letting Rizzo hit first, mostly because his team's offense has been stuck in a season-long rut and no one else has stepped up in replacing Dexter Fowler at the top of the order.
"If everything is in place and in order, I probably would not have done that," Maddon said.
Rizzo joked with teammates before the game -- and actually texted Fowler, as well -- that he was going to hit a first-pitch home run, but he settled for the second pitch; then he walked with the bases loaded and doubled home another run, all in the first three innings.
After the Cubs' offense came alive -- behind a seven-run second inning -- Maddon indicated Rizzo would be leading off again on Wednesday.
"You know what?" Rizzo asked. "Let's go on a run now. That would be great. Just keep winning. Hopefully, this can be the start of something, but it's just one game."
Rizzo is the first Cubs first baseman to lead off a game with a home run since Rick Monday in 1976. His 461-foot shot also was the longest home run to begin a road game since ESPN started tracking them in 2009.
The blast helped back starting pitcher Jon Lester, who won his 150th career game.
"Personal stuff is always cool, whatever," Lester said. "That was a big win for us tonight, on a lot of levels -- pitching, offense, baserunning, defense, the whole deal. It was a good night for us."