The No. 3-ranked Djokovic had nine double-faults and 52 unforced errors in his 3-6, 6-1, 6-1, 6-3 win Wednesday night over Marco Chiudinelli, the Swiss player who was playing in his first Australian Open.
"I was well aware of his quality, and he played extremely well, especially in the first set and the start of the second," Djokovic said. "I was very lucky to get two sets to one up."
"This court is most special because I won my only Grand Slam here," the 22-year-old Serb said of Rod Laver Arena, where he beat Federer in the semifinals en route to the 2008 title. "It has the nicest possible memories."
Djokovic will next play Uzbekistan's Denis Istomin, who beat Michael Berrer, of Germany, 7-5, 6-3, 6-4.
Sixth-seeded Nikolay Davydenko, who rarely gets onto the center court at this stage of a Grand Slam, had a 6-3, 6-3, 6-0 win over Ukraine qualifier Illya Marchenko.
Juan Martin del Potro, the Argentine who upset Roger Federer to win last year's U.S. Open, held off James Blake 6-4, 6-7 (3), 5-7, 6-3, 10-8, while defending champion Rafael Nadal won in straight sets.
On the women's side, Justine Henin held off fifth-ranked Elena Dementieva 7-5, 7-6 (6), winning the last three points of the tiebreaker to clinch a second-round victory worthy of a final.
She ended it on her second match point -- 24 minutes after she missed her first chance against the Olympic champion.
Former No. 1-ranked Ana Ivanovic, of Serbia, extended her run of poor results in a second-round 6-7 (6), 7-5, 6-4 loss to Gisela Dulko of Argentina.
In other women's results, No. 10 Agnieszka Radwanska, of Poland, advanced 6-0, 6-2 over Russia's Alla Kudryavtseva and No. 32 Carla Suarez Navarro, of Spain, had a 6-1, 6-4 win over German Andrea Petkovic.