Blake, from the United States, was ousted in 59 minutes by 10th-seeded German Tommy Haas, who posted a 6-4, 6-2 victory.
The loss hurt Blake's chances of making the field of eight for the upcoming Tennis Masters Cup in Shanghai, but sixth-seeded Spaniard Tommy Robredo sewed up a spot in that tournament with a 6-5, 7-6 (7-1) victory over France's Paul-Henry Mathieu.
No. 9 Mario Ancic, from Croatia, swept past France's Julien Benneteau 6-3, 6-1, while eighth-seeded and defending Paris Masters champion Tomas Berdych eliminated American Robby Ginepri, 6-3, 6-3.
Also, 14th-seeded Finn Jarkko Nieminen overcame Russian Teimuraz Gabashvili, 4-6, 7-6 (8-6), 6-2; 17th-seeded Slovak Dominik Hrbaty beat 13th-seeded Brit Andy Murray, 7-6 (8-6), 6-0 and unseeded Russian Marat Safin advanced via walkover when 16th-seeded Frenchman Richard Gasquet decided against playing due to a right thigh injury.
Swim Week Miami Beach 2014 [PHOTOS]