Djokovic, playing for the first time in six weeks after a back injury in the Davis Cup semi-finals left him in lying in agony on court in Serbia, finally overcame the in-form Belgian 6-2, 4-6, 7-5 to progress to the second round.
The world number one who took the Basel title in 2009 but lost the final a year ago to Roger Federer, walked onto the court wearing a Batman Joker Halloween mask, but got a fright of his own as he faced down Malisse, ranked 47 in the world.
The Serb ended with a break of the 30-year-old Belgian in the final game after losing his way as he served for victory leading 5-3 in the third set.
Djokovic dropped serve on a fifth break point, his seventh double fault but found a way to win three games later.
"I'm only just back from the biggest injury of my career," said the winner of ten titles in 2011. "It was a big ask for me to have played really well.
"I could do nothing for four-and-a-half weeks, I've only been hitting for a week-and-a-half. That's not enough to play at my best. I've lost rhythm.
"I had too many errors and too many double-faults. But I'm happy just to be playing tennis again. I hope to build on this performance."
The loser of just two ATP matches this season - plus one in the Davis Cup semi-final against Argentina - improved to 65-3 on the season.
Djokovic is the only man other than Federer to win the Basel title in the past five years.
The chances for Mardy Fish to play in his first ATP season finale may have been badly compromised as the American suffered a hamstring injury just 11 minutes into his opening match.
Fish was leading compatriot James Blake 1-0 in the opening set when he was forced to retire.
"I didn't see anything. He suddenly started grabbing at his hamstring and had to call the trainer," said Blake.
"It's worrisome that it appeared to happen on one shot and not over the course of a few days.
"But Mardy is doing the cautious thing, he's gone for an MRI and we will have to see."
The retirement could mean the end of Fish's hopes of winning a place in the World Tour Finals in London from November 20th.
The 29-year-old stands a provisional eighth in the race for the eight-man field, with three places still up for grabs.
Two Swiss players moved into the second round, with 2006 semi-finalist Stanislas Wawrinka leading the way with his defeat of Croatian Ivan Dodig 6-4, 6-4. Qualifier Michael Lammer put out experienced Russian Mikhail Youzhny 6-4, 6-3.
Wawrinka will next face either second seed Andy Murray or Dutchman Robin Haase.
Roger Federer was honoured as the all-time best of the Basel event since it began in 1970 and among other things had his picture painted during the ceremony in five minutes by a speed artist.
The Swiss drew 31,000 of 40,000 online public votes, with Djokovic receiving 3,000-odd and Björn Borg a mere 1,000 or so.