The legend of the Masked Mamba grew with Bryant's third straight stellar performance since Dwyane Wade broke his nose. Wade managed just 16 points before fouling out midway through the fourth quarter.
"He knew I was going to be ready regardless," Bryant said.
Metta World Peace scored 17 points while leading a solid defensive effort for L.A., who have won 17 of their last 18 home games. Andrew Bynum chipped in with 16 points and 13 rebounds.
The Lakers never trailed in the final 44 minutes, snapping a four-game skid in Bryant's head-to-head matchup with Wade's Heat.
LeBron James had 25 points, 13 rebounds and seven assists for Miami, who lost on the final two stops of their three-game trip.
The Lakers win was the second game in a marquee doubleheader on Sunday. The Boston Celtics beat the New York Knicks 115-111 at TD Garden earlier in the day.
Boston's Rajon Rondo had his second triple-double in three games, finishing with 18 points, 20 assists and a career-high 17 rebounds.
The Associated Press contributed to this report.