The hosts made a strong start when an unmarked Keisuke Honda headed in Hiroshi Kiyotake's free kick in the 11th minute to give the four-times Asian champions a 1-0 lead in a Group B match played in front of a sellout crowd of 65,000.
The Emiratis, who beat the Blue Samurais in last year's Asian Cup quarter-finals in a penalty shootout, equalised nine minutes later when Khalil, the Asian player of the year, netted.
Japan goalkeeper Shusaku Nishikawa could only tip Khalil's curling 25-metre free kick into the top corner.
Former Manchester United player Shinji Kagawa should have given Japan the lead in the 26th minute but shot wide from a rebound after UAE goalkeeper Khalid Eisa had saved Honda's header.
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Eisa also tipped over a long-range effort from Ryota Oshima after the interval.
Khalil made it 2-1 from the penalty spot in the 54th minute after Ismail Al Hammadi was brought down.
Japan stepped up the pressure and went close to levelling when Shinji Okazaki's header hit the bar.
Eisa pulled off another wonderful save to deny Japan in the 77th minute although television replays suggested substitute Takuma Asano's shot had crossed the line.
"It's a terrible, terrible result and I don't know why this has happened," Japan coach Vahid Halilhodzic told the Kyodo news agency. "We made lots of chances but conceded ... two goals that could have been easily prevented.
"It is difficult to accept how the referee ran the game but we still have nine matches and it is not over yet."
The UAE now face Asian champions Australia in Abu Dhabi on Tuesday while Japan travel to Bangkok for their next match against Thailand.
Australia also made a confident start to their campaign with a 2-0 victory over Iraq in Perth.
(Reporting by Sudipto Ganguly; Editing by Tony Jimenez)
