Djokovic, who had been idle since capturing the Australian Open title last month, blew past German Cedrik-Marcel Stebe 6-4, 6-2 on the hardcourts at Dubai Tennis Stadium. The Serbian star currently holds three of the four Grand Slam titles.
The high-flying Djokovic topped Roger Federer in last year's marquee Dubai finale to capture his third straight title here.
The highest-ranked American, world No. 8 Mardy Fish, joined Djokovic in the second round by blitzing overmatched German Andreas Beck 6-1, 6-1 in 57 minutes. The sixth-seeded Fish rebounded from a stunning tournament-opening loss at the hands of unheralded Frenchman Albano Olivetti last week in Marseille.
Also on Day 1 in Dubai, Djokovic's 20-year-old younger brother Marko, a wild card this week, lost to Kazakhstani qualifier Andrey Golubev 6-3, 6-2.
"In the end, he has to face this, I guess, pressure in a way for having Djokovic surname," Djokovic said of Marko, who struggled on Monday. "All over the world where he plays tennis, I guess he has to face this pressure that is not necessary for him at this age. It's his burden, and he's very committed. He wants to succeed in tennis."
Other opening-round wins came for Slovak Lukas Lacko and Czech Lukas Rosol. Lacko saved six match points before outlasting Ukrainian wild card Sergei Bubka in three sets, including a 16-14 third-set tiebreak. Bubka is the son of legendary pole-vaulter Sergey Bubka.
Tuesday's schedule features matches for six of the top-10 players in the world, including the second-seeded four-time Dubai champion Federer and third-seeded Andy Murray. Federer will encounter Frenchman Michael Llodra, who was last week's Marseille runner-up to Juan Martin del Potro, while Murray will meet left-handed German qualifier Michael Berrer.
Federer and Djokovic have combined to win seven of the last nine Dubai championships.
Also slated for Day-2 action are Jo-Wilfried Tsonga, Tomas Berdych, Janko Tipsarevic and an eighth-seeded del Potro, who will be opposed by Ukrainian Alexandr Dolgopolov. Tsonga will battle fellow former Aussie Open runner-up Marcos Baghdatis.
The 2012 Dubai champ will collect $409,170.