Lee Nailon scored a career-high 32 points for the Hornets but had two shots blocked by Bosh in the final 1:44.
"That was the best thing I did all night. If I don't block Lee's shots we're probably down five or three points down the stretch," Bosh said. "I just got two big blocks and we took advantage."
Morris Peterson had 25 points and 10 rebounds for Raptors, who are 7-7 since trading Vince Carter to New Jersey on Dec 17. Jalen Rose added 19 points off the bench, and Bosh finished with his seventh straight double-double.
The Raptors are hoping to rebuild around the second-year forward.
"We talk to Chris about it every day," Toronto coach Sam Mitchell said. "You can affect the game in a lot of ways, you just don't have to score. He has to rebound, block shots and he has that ability. We ask a lot of a 20-year-old."
New Orleans point guard Baron Davis left late in the third quarter with a bruised right ankle and did not return. Davis had 15 points and 11 assists.
"It really hurt us in that last quarter," New Orleans coach Byron Scott said. "We didn't have anybody to penetrate their defense."
Scott expressed frustration that his message isn't getting through. The Hornets are an NBA-worst 5-31.
"Either we are not listening or hearing or we're not bright enough to understand what I'm saying," Scott said. "We're still last in 3-point percentage, and we hoist up 28 tonight. That's not a way to win a game."
Nailon attempted a driving layup with less than two minutes left, but Bosh blocked it and Rose ran down the floor and made a fast-break layup to cut New Orleans' lead to a point. Rafer Alston's two free throws with 1:15 left gave Toronto its first lead since the second quarter.
Nailon then appeared open for a short jumper, but Bosh blocked his attempt with less than a minute left. Alston followed with a driving layup, giving Toronto a 98-95 lead with 13 seconds to go.
P.J. Brown made 1-of-2 free throws to cut the lead to two with 11 seconds remaining, but Rose made two to make it 100-96.
Dan Dickau converted a three-point play to cut it to one with six seconds left, but Alston made two more free throws and Dickau missed badly on a 3-point attempt that could have tied it at the buzzer.
The Hornets led for most of the game but didn't recover after Davis left with 1:51 left in the third.
Nailon went 14-for-20 from the field. He also had eight rebounds and six assists. ... ... The Raptors have won three straight at home and six of seven. ... The Raptors are 13-5 at home. ... Toronto is 9-0 when Bosh scores 20 or more.