The routine win on Friday in just over an hour was straightforward for Nadal, a two-time Miami finalist looking to stop the rot and win his first title since Rome last May.
"It was a good start for me," said Nadal. "Playing Dent is always a difficult match because you don't have rhythm.
"I had small chances on the return - only a few. I converted, and I had three breaks against his unbelievable serve."
The Spaniard moved through despite a painful wisdom tooth which must be removed after his tournament ends.
"I'm happy for the victory. It was a comfortable win against a difficult opponent."
But there was high drama on court for most of the afternoon as Belgium's pocket rocket Olivier Rochus pounded out a 6-2, 6-7 (7/9), 6-4 opening upset over Novak Djokovic to knock the second-seeded Serb out.
The victory marked the second win over a top 10 player in Miami for Rochus, who stands just 1.67 metres and ranks 59th in the world.
"He made me run a lot, the points were long, I'm exhausted," said Djokovic. "He was playing really well today, He deserved the win.
"He was motivated to win against a top player and had nothing to lose. He coped well."
Nadal improved to 13-3 on the season and 18-6 in Miami, where he lost finals in 2005 (to Roger Federer) and 2005 (to Nikolay Davydenko).
Djokovic and Rochus, were delayed for two and a half hours at their start as a rainstorm swept over Key Biscayne.
They were also interrupted for 52 minutes after the ninth game of the second set by more bad weather.
Rochus fought like a tiger throughout the contest, sweeping the first set and battling hard in the second under a barrage of break points.
The underdog was broken leading 5-4 and serving for the win in the third, but the Belgian broke back for victory as Djokovic sailed a forehand over the baseline after almost three hours on court plus the nearly one-hour rain delay.
"It was a very close match, so I knew I could do something," said the surprised winner. "I just tried my best.
"I had played well in the first round, so I was feeling confident. But of course I never expected to win."
The frustrated Djokovic was left to ponder 10 double-faults and six broken serves.
Djokovic, the 2007 champion, lost his fourth match of the season against 15 wins less than a month after lifting his 17th career title in Dubai.
The 22-year-old Serb, runner-up last year to Andy Murray, stands 1-3 against Rochus.
It was a second straight disappointment for Djokovic after losing in the Indian Wells fourth round last week to eventual champion Ivan Ljubicic.
"I didn't feel great on the court and everyone could see," said Djokovic. "Life goes on. I'll try to make up for this loss.
"I wasn't attacking, I was waiting for him to make shots. It wasn't the right approach."
Two other seeds advanced, with 12th seed Juan Carlos Ferrero moving through as Austrian Daniel Koellerer retired while trailing 4-0 and 15th seed David Ferrer scoring a 6-2, 6-4 victory over Frenchman Michael Llodra.
A pair of Americans were bundled out as Frenchman Jeremy Chardy stopped Sam Querrey 4-6, 6-4, 6-2 and Brazil's Tomaz Bellicci added to the misery of veteran James Blake with a 3-6, 6-1, 6-2 defeat.
Women's seeds fared better with wins all round. Holder Victoria Azarenka, seeded fourth, beat Romanian Alexandra Dulgheru 6-3, 6-2 while number seven Jelena Jankovic backed up her weekend title at Indian Wells 6-4, 6-0 triumph over Mariya Koryttseva.
Australian ninth seed Samantha Stosur staged a fightback to take out Spain's Carla Suarez Navarro 4-6, 7-5, 6-2.
US Open winner Kim Clijsters put last week's early defeat behind her with a 6-1, 6-1 win over Czech Petra Kvitova.
Italian number 15 Francesca Schiavone defeated Alize Cornet of France 6-3, 6-2.