It was the ninth consecutive victory for the Heat, who at 28-7 are off to their best 35-game start in franchise history.
Dwyane Wade added 33 points and 10 assists for the Heat in their first game since the All-Star break. Miami hadn't played since a 102-88 victory at home against the New York Knicks last Thursday.
The Heat were without Bosh because of a death in his family. The All-Star was also expected to miss Friday night's game at Utah, but it is not yet known whether he will play Sunday when Miami visits the Los Angeles Lakers.
Spoelstra said he approached James at shootaround, saying he needed a little bit of everything from his star.
"Really, it was as simple as this: 'We need a Magic Johnson-type, not necessarily performance, but awareness,' " Spoelstra said. "Man, he really took the challenge. It's his ability to do all these different things in the course of one game."
James said he, in turn, told his teammates that he was going to guard everyone.
"We had a big piece of our team out, so I definitely had to step up my game to bring home this win," he said.
LaMarcus Aldridge had 20 points for the Blazers, who were coming off a 104-95 loss to the Denver Nuggets on Wednesday night. Portland (18-18) has lost eight of its past 12 games.
It was never much of a contest, and the Blazers trailed by as many as 25.
Aldridge, coming off his first All-Star appearance, was clearly frustrated.
"I'm at the point where we can't keep talking about what we need to do," he said. "We have to go out and do it."
Before the game, the Blazers activated center Joel Przybilla, who was signed by the team earlier this week.
Przybilla, who spent more than six seasons in Portland before he was traded to Charlotte last season, had not played since last March. An 11-year NBA veteran, the 7-foot-1 center finished with four points, six rebounds and two blocked shots in 19 minutes.
A fan favorite, he was treated to a standing ovation by the Rose Garden crowd.
"Miami is on a mission. They are focused on winning a championship," Przybilla said afterward. "And we want to get where they are, we want to get to the level they're at."
The Blazers jumped out to an early 14-6 lead, but the Heat came back to tie it on Wade's lob pass to James for the dunk. James and Wade combined for all of Miami's points to that point.
The Heat extended the lead to 30-21 on Mario Chalmers' jumper. They kept the Blazers at bay the rest of the half, going up 45-34 on Udonis Haslem's 15-foot jumper before taking a 60-42 lead into the break. James and Wade accounted for 41 of the team's points.
The second half was more of the same. James went to the bench in the fourth quarter with the Heat still holding a sizable lead. But the Blazers chipped away a bit, coming to within 91-78 on Wesley Matthews' reverse layup.
James' break was brief and the Blazers got as close as 95-85 on Nicolas Batum's 3-pointer with 4:35 left. James answered on the other end with a 3-pointer of his own.
James has scored 30 or more points in 15 games this season. Wade has scored at least 20 points in 10 consecutive games.
Last season, James scored 44 points against the Blazers, a record-high for an opponent at the Rose Garden, in a 107-100 overtime victory for the Heat. The road team has won the last five games in the series.
Blazers coach Nate McMillan said he was proud that his team didn't "fold up the tent," when it was clear they weren't going to win.
"I don't think our guys did that tonight. They kept scrapping," he said. "We had a slow second quarter. That was the big quarter for us. But for the most part, I thought we kept competing."
- Spoelstra was selected as the NBA's Eastern Conference coach of the month on Thursday after leading Miami to a league-best 11-2 record in February. It's the third time he has earned the honor.
- Former Blazer Scottie Pippen was at the game.
- Batum cut his lip in the second half but returned.
- The game was the only meeting between the Heat and the Blazers this season.
- Portland placed C-F Kurt Thomas on the inactive list because of a concussion he sustained the night before in Portland's loss at Denver.
- It was Miami's fifth consecutive road victory.