The fourth-seeded Wozniacki recorded three service breaks en route to her 6-4, 6-4 decision over No. 10 seed Williams, which took 95 minutes to complete.
She goes on to face another former top-ranked player, second-seeded Maria Sharapova, who advanced with a 6-3, 6-0 rout of China's Li Na Tuesday.
The Russian broke the Li seven times in the victory, and will seek to reach her third final in four events so far this season.
Sharapova, who lost to current world No. 1 Victoria Azarenka in last year's Miami finale, owns a 3-2 career mark against Wozniacki.
The 26-0 Azarenka will face seventh-seeded Marion Bartoli in one of Wednesday's quarterfinal matches while fifth-seeded Agnieszka Radwanska will take on three-time Miami champ Venus Williams in the other.
Swim Week Miami Beach 2014 [PHOTOS]