The best of men's and women's tennis was on display at Crandon Park with the winners of over 30 grand slam singles titles all in centre court action.
After Federer and Djokovic's successes, Venus Williams registered a straight sets win and Li Na advanced in a walkover, it was left to defending champion Murray to provide a bit of late night drama, taming Australian Matthew Ebden 3-6 6-0 6-1 as the clock approached midnight.
Murray, who split with coach Ivan Lendl earlier in the week, got the contest off to an unsteady start when Ebden broke him at the first opportunity and then held serve to quickly jump in front 3-0 on his way to easily taking the opening set.
After storming through the second set, Murray was broken at the start of the third which sent the Briton into a towel tossing rage as he berated himself.
The chastising had the desired result as the sixth seed immediately broke back to get on level terms and raced through the next five games to clinch a convincing victory.
"You do what you do to win a match," said Murray. "It's not always about how you play or how calm you are on the court, it's about winning the tennis match. That's what matters.
"I won the next six games after that so maybe it nothing to do with it, maybe it helped. I just got on with it and won the match."
After a year's absence, fifth seeded Federer celebrated his return to the Miami hardcourts with a clinical 6-4 7-6 (4) win over towering Ivo Karlovic while world number two Djokovic launched his bid for a fourth Miami title in impressive fashion, dispatching Frenchman Jeremy Chardy 6-4 6-3.
A twice winner at Crandon Park, Federer did not visit Miami last year, taking an extended layoff before starting his season. But he looked quite at home, needing just 74 minutes to slay the 6-foot, 11-inch (2.11m) Croatian in a slugfest that featured just one break of serve.
"I was able to play a very clean match on my service games throughout, make sure I had a lot of first serves in, make sure I stayed aggressive from the baseline," said Federer. "I think it worked really well, hardly any unforced errors.
"There are no long rallies. It's just like more penalty shootout, like in soccer.
"It's about quick reaction, not getting frustrated and feeling that the returner is the one who has got less pressure."
GOOD SERVES AND GOOD SHOTS
Federer, who had been dismissed as a fading force following last year's disappointing campaign, has hit back at his critics on the court, clinching the 78th title of his career in Dubai earlier this month, while reaching the finals in Brisbane and last week in Indian Wells, where he lost to Djokovic.
It was another dominating performance by the re-energised Swiss maestro, particularly in the opening set where he committed a single unforced error.
Federer broke to open the match on a Karlovic double fault and did not surrendered a point on his serve until attempting to close out the set at 40-0.
The 32-year-old Swiss continued his near perfect play in the second set finishing with a total of three unforced errors but could not break the big-serving Croatian, who blasted 13 aces past the 17-time grand slam winner.
But Karlovic's big serve was not able to save him in the tie-break as Federer coolly clinch the match 7-4.
Djokovic, riding the momentum from his victory at Indian Wells into South Beach, jumped out to a 4-1 lead in the opening set before breaking Frenchman Chardy to secure a 1-0 lead.
There was only one break in the second set and that went to Djokovic, who nosed in front 5-3 before serving out for victory.
"It's a straight sets win and when I was supposed to play my best and come up with some good serves and good shots, that's what I have done in both sets," said Djokovic. "That's what matters the most to me."
In other action, fourth seeded Spaniard David Ferrer and ninth seeded Frenchman Richard Gasquet both had straight sets passages to the next round.
Ferrer, who lost last year's final to Andy Murray, returned to action after sitting out the Masters series event in Indian Wells with a left abductor strain and showed no hint of rust as he cruised past Russian Teymuraz Gabashvili 6-4 6-0.
Gasquet was given a tougher task but eventually dispatched 83rd ranked Colombian Alejandro Gonzalez 7-6 (7) 6-4.