Djokovic has been the world's most consistent player this season, going 54-1. Last week in Montreal, he became the first to win five ATP Masters Series titles in one season. He improved to 30-0 on hard courts by taking advantage of Harrison, a 19-year-old from Florida who broke his serve to open the match but then fell apart. Harrison had 20 unforced errors in the first set alone.
Djokovic would like to keep his winning streak intact heading into the U.S. Open, where he lost the title match to Rafael Nadal last year.
"Performing the best tennis is the priority in New York," he said. "But I'm not playing the matches in this tournament just to get some practice. I'm playing to win."
Earlier, second-seeded Nadal beat qualifier Julien Benneteau 6-4, 7-5 despite burns on the index and middle finger of his right hand, which the left-hander uses to steady his backhand shot.
Nadal said he touched a hot plate at a restaurant a few days ago. Both fingers were wrapped in gauze for protection.
"The plate was very hot and I got burned," he said.
Also Wednesday, fourth-seeded Andy Murray beat David Nalbandian 6-4, 6-1; fifth-seeded Spaniard David Ferrer rallied past Grigor Dimitrov of Bulgaria 4-6, 6-1, 7-5; No. 6 Gael Monfils of France was leading 4-6, 6-3, 4-0 when Ivan Dodig of Croatia retired; seventh-seeded American
Mardy Fish defeated Russian Nikolay Davydenko 6-0, 6-2; ninth-seeded Nicolas Almagro of Spain advanced with a 6-3, 5-7, 7-6 (2) win over Ivo Karlovic of Croatia; No. 10 Gilles Simon of France rallied past Janko Tipsarevic of Serbia 6-7 (3), 6-2, 6-3; 12th-seeded Frenchman Richard Gasquet defeated South Africa's Kevin Anderson 7-6 (4), 6-4; and American Alex Bogomolov Jr. upset No. 15 Jo-Wilfried Tsonga of France 6-3, 6-4.
Information from The Associated Press was used in this report.