"They're playing great and they got hot guys," Chacin said. "You got to be careful."
Chacin (6-4) won a matchup of rookie left-handers, outpitching John Koronka. Chacin allowed five hits, struck out a career-high six and was backed by two double plays.
The Blue Jays were struggling after losing series in Seattle and Oakland, but they won for the fourth time in 11 games.
The Cubs, meanwhile, had won nine of 10 and went 6-1 on their West Coast swing to Los Angeles and San Diego.
"The guy threw a good game against us. A major difference is the fact we didn't know him," Cubs manager Dusty Baker said. "He probably knew more about us than we did him."
Johnson's fifth homer came in the second and was set up when the Cubs didn't make a play on a bunt.
"We didn't know the speed of McDonald," Baker said.
The relay to first didn't get Chacin, either.
"Chacin did his thing pitching and he got down the line on the bunt, hustling," Toronto manager John Gibbons said. "He shut down a hot team."
After McDonald stole third, Johnson homered to left-center on a 3-2 pitch for a 4-0 lead.
"To hit a home run in Wrigley Field is a pretty good feeling," Johnson said. "I didn't even realize it until I sat down in the dugout and looked out onto the field and watched the rest of the inning."
Vinnie Chulk gave up a leadoff homer to Aramis Ramirez in the ninth before Miguel Batista got three outs for his 10th save in 11 chances. With runners at the corners, he got Jose Macias to ground into a game-ending double play.
"We saw (Chacin) on film. But today he was pitching backward compared to what we'd seen," Cubs catcher Michael Barrett said. "We had a good scouting report, but he didn't do anything we'd seen until he got in trouble. We really didn't put pressure on him all game."
Aaron Hill hit a two-out RBI single in the first to score Vernon Wells, who doubled.
The Cubs loaded the bases with one out in the second when Koronka worked a walk after an error and a single. But Jerry Hairston hit into a 6-4-3 double play.
"After I walked the pitcher, I felt bad. I threw a sinker down and I was able to get out of that inning," Chacin said.
Koronka (1-1) allowed six hits and four runs in six innings and was also pitching at Wrigley for the first time. He said he wasn't as nervous as he was anxious. And he thought he could get McDonald at second on the bunt.
"I heard a couple of yells going to second. I think we had him. I should have put a little more on it," Koronka said. "But I wanted to make an accurate throw and it ended up we didn't get him at first, either."
- Eight of Johnson's last 15 hits have been for extra bases.
- It is the second interleague meeting between the teams. Toronto won two of three at home in 2003. Johnson homered twice in the series finale that season, won by the Blue Jays 5-4 in 10 innings.
- Derrek Lee, leading the majors with a .385 average coming into the game, went 1-for-3 and was hit by a pitch.