Djokovic has struggled in the past with the 6-foot-10 (2.08m) Isner's bombing serve on the hardcourts of the California desert.
But the reigning Australian Open champ got the best of his opponent in the key tiebreaker.
"John has one of the best serves in the game," Djokovic said. "It was difficult to hang in there mentally.
"He had chances in the second set but I managed to get through in straight sets."
Djokovic booked a quarter-final clash with 35th-ranked Bernard Tomic of Australia.
In 2012, Isner upset Djokovic 7-6 (9/7), 3-6, 7-6 (7/5) in the semis, a defeat Djokovic avenged last year by beating Isner 7-5, 6-7 (2/7), 6-1 to reach the final.
Djokovic now has a 6-2 advantage in career meetings, with nine of the sets going into tiebreakers. Isner has won six of those, so Djokovic felt fortunate to squeak through this time.
"With his size and his serve he can beat anyone so I am very pleased with the victory which for me is very big," Djokovic said.
Djokovic hammered seven aces and saved both break points he faced in the one hour, 31 minute match.
"The first set was really good tennis," Federer said. "I played well throughout and was able to serve better than Jack today."
In the quarter-finals, the Swiss second seed will face ninth-seeded Czech Tomas Berdych, a 6-2, 4-6, 6-4 winner over compatriot Lukas Rosol.
"The opponents are getting tougher as you get into the back end of the tournament," Federer said.
Federer and Berdych have met 18 times with the Swiss holding a 12-6 lead.
World number three Rafael Nadal rolled over France's Gilles Simon 6-2, 6-4.
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