The two-time Aussie Open champ Djokovic has never reached a Wimbledon final, having reached semifinals here in 2007 and last year.
The 24-year-old Djokovic was riding a 43-match winning streak this year before Federer topped him in the semifinals at the French Open three weeks ago, which denied Djokovic a shot at the world No. 1 ranking. The Serbian slugger has titled in seven of his eight tournaments in 2011.
"Mentally, I do have a different approach to Wimbledon than I had years before. It's obvious because of the winning streak that I had, the confidence that is very high," Djokovic said. "It makes it easier to step on the court because you believe in yourself. You know that you're one of the best players in the world and you know that you can win against anybody."
Djokovic's third-round opponent will be former Wimbledon semifinalist Marcos Baghdatis.
Federer blew past Mannarino in 1 hour, 28 minutes, as he fired 11 aces among his 38 winners.
The 29-year-old Federer has held his serve all 28 times to this point in the fortnight.
The former world No. 1 Federer owns a men's record 16 major titles, including six of the last eight here at Wimbledon. Up next for the all-time great will be long-time nemesis David Nalbandian, who has beaten the super Swiss eight times in 18 tries on the ATP circuit.
An unseeded Hewitt stunned the two-time French Open runner-up Soderling by jumping out to an unexpected two-sets-to-love lead before the big Swede charged all the way back for a 6-7 (5-7), 3-6, 7-5, 6-4, 6-4 victory under the roof on Centre Court, as there was some on-and-off rain throughout the day.
The match ended after 3 hours, 54 minutes when Hewitt netted one final forehand, as Soderling broke the Aussie to end the bout. The Swedish slugger tallied 31 more winners than Hewitt (75-44), including 28 aces. Soderling also wound up with twice as many breaks (4-2) as his Aussie counterpart.
This was Soderling's third career victory after trailing by two sets.
The oft-injured former world No. 1 Hewitt captured a Wimbledon championship back in 2002, marking his second Grand Slam title. He also won the 2001 U.S. Open.
This marks a dejected Hewitt's earliest Wimbledon loss since 2003.
"It's hard at the moment. But in the end, I feel like I hit the ball pretty well," Hewitt said. "I hit it a lot better than I did a couple days ago and I needed to against a guy like Soderling."
"It's just one of those days," Hewitt added. "The roof closed I think helped his game, as well."
In a tremendous match on Court 1, 12th-seeded Jo-Wilfried Tsonga snuck past ultra-talented Bulgarian Grigor Dimitrov 6-7 (4-7), 6-4, 6-4, 7-6 (10-8). The 20-year-old Dimitrov is one of the most promising young players on the ATP World Tour.
Tsonga, who smacked 19 aces en route to victory, needed six match points to finally stop Dimitrov, as the Frenchman struck a backhand winner past a diving Bulgarian to end the electric affair in 3 hours, 33 minutes.
The flashy Tsonga will battle fellow former Aussie Open runner-up Fernando Gonzalez of Chile on Saturday. The former top-10 star Gonzalez, on the mend from hip surgery, moved on with a 6-4, 6-4, 6-4 handling of South African Rik De Voest.
Former U.S. Open champion Juan Martin del Potro dropped the first set of his second-round match here on Wednesday before play was called because of darkness, but the big Argentine returned to the court Thursday to slap around diminutive Belgian Olivier Rochus for a 6-7 (7-9), 6-1, 6-0, 6-4 decision. The 6-foot-7 del Potro is a former world No. 4 who is seeded 24th at this particular fortnight.
Up next for del Potro will be 15th-seeded former top-10 Frenchman Gilles Simon.
The 2002 Wimbledon runner-up to Hewitt, Nalbandian, joined his fellow Argentine del Potro in the round of 32 with a 6-3, 3-6, 6-4, 6-4 victory over Austrian Andreas Haider-Maurer. The oft-injured Nalbandian is seeded 28th here.
Towering American John Isner exited the draw when 16th-seeded Spaniard Nicolas Almagro topped him 7-6 (7-3), 7-6 (7-5), 6-7 (5-7), 6-3 on Court 18, where the 6-foot-9 Isner beat France's Nicolas Mahut in last year's record-smashing first-rounder that was played out over three days and completed in 11 hours and five minutes.
Meanwhile, 14th-seeded Viktor Troicki went by way of the upset, as Taipei's Yen-Hsun Lu upended the Serb 7-6 (7-5), 6-4, 6-4; 18th-seeded Russian Mikhail Youzhny leveled up-and-coming Indian Somdev Devvarman 6-2, 6-4, 6-4; 19th- seeded Frenchman Michael Llodra got past Brazil's Ricardo Mello 6-2, 4-6, 6-2, 6-3; talented Belgian Xavier Malisse took out 20th-seeded German Florian Mayer 1-6, 6-3, 6-2, 6-2; and Slovakian Karol Beck bounced 26th-seeded Spaniard Guillermo Garcia-Lopez 7-6 (7-5), 6-4, 3-6, 6-4.
The aforementioned Baghdatis, seeded 32nd this year, got past Italian Andreas Seppi 6-4, 7-6 (7-4), 7-5. Seppi was fresh off his grass-court title in Eastbourne. Baghdatis is a former Aussie Open runner-up.
American teenager Ryan Harrison was leading seventh-seeded Spanish grinder David Ferrer 7-6 (8-6), 1-6, 6-4, 2-4 when play was suspended for the day due to darkness.
The third round will get underway on Friday, as top-seeded Rafael Nadal, fourth-seeded Andy Murray, eighth-seeded Andy Roddick and the formidable del Potro will be among those taking to the courts.
The reigning Wimbledon, French Open and U.S. Open champion Nadal will meet Luxembourg's Gilles Muller, who upset the 10-time Grand Slam champion in the second round at the All England Club back in 2005.
The Aussie Open runner-up Murray, of Great Britain, will battle former top- five Croat Ivan Ljubicic, while the three-time Wimbledon runner-up Roddick will be opposed by Spaniard Feliciano Lopez, and the 2009 U.S. Open champion del Potro will face Simon.
Sixth-seeded 2010 Wimbledon runner-up Tomas Berdych, ninth-seeded Frenchman Gael Monfils and 10th-seeded American Mardy Fish will also see action on Friday.