He posted a 13-under 197 total, a tournament record low 54-hole score, with Englishman Tyrrell Hatton (66) the closest challenger on nine-under, and a group of five players six strokes back in a tie for third.
Fowler won the European Tour’s Abu Dhabi Championship in January last year, but has not triumphed on the PGA Tour since 2015, when he clinched his second and third career victories.
He is 0-4 when holding the lead starting the final round on tour, though he has never had such a big cushion.
"I do have a lot of work to do tomorrow but a four-shot lead is nice," Fowler told reporters.
"(It) can obviously go away very quickly too but when you do have that cushion it does give you the opportunity to accept mistakes. If you're playing from three or four shots behind, you can't make mistakes.
"I'll be out front and in control, and with the way I feel about the game, the way I've been swinging, I'm looking forward to it."
Fowler was not quite firing on all cylinders early on Saturday but improved as the round progressed.
"I've hit a lot of fairways right down the middle and it gives me a lot confidence. Tomorrow just make sure we settle in a little quicker, just trust it and have some fun."
After ideal conditions on Saturday, the forecast on Sunday calls for a stiff breeze, which could create drama over the water-lined closing stretch.
"This course can jump up and bite you at any time so I need to stick to the game plan," Fowler said.
"I love playing in the wind."
Fowler distanced himself from Hatton by sinking a ten-foot birdie putt at the par-four 16th and then picking up another birdie at the par-five 18th after a blistering 340-yard drive.
Hatton, who will make his Masters debut this year, could have been closer to the lead had he not bogeyed the penultimate hole. He also failed to birdie the last.
(Reporting by Simon Evans in Miami; Editing by Andrew Both)
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