The six-under-par effort at Sheshan International left the 31-year-old Scot sitting joint-third, two shots behind Swedish pacesetter Rikard Karlberg.
Knox, who is bidding to become only the second player after Tiger Woods to retain a WGC title, featured in the best scoring group of the day.
His two playing partners, Rickie Fowler and Paul Casey, signed for 65 and 67 respectively as the trio finished the round a combined 18-under-par.
“The first round is never my strongest, so I’m delighted to get off to a flyer and shoot six under,” admitted Knox, who, after teeing off at the tenth, lit the fuse on his effort with four birdies in a row from the 14th.
He then picked up further shots at the third and seventh as he took up where he’d left off 12 months ago when winning with a 20-under-par total.
“I didn’t put any pressure on myself, but you only get once shot at your first defence, so I want to make sure I have a good time over the next three days,” he added.
“The conditions were just like this on Sunday last year - very dark and dreich, as the Scots would say, with a little mist and rain.
“The course played long today, which is fine for me. If it’s lift, clean and place, as long as I’m on the fairway, I can compete around here.
“So it’s all about my tee shot to set up my iron game.”
Knox may be the man defending the title this week but he reckoned the majority of the fans out watching his group were there to see one of his playing partners.
“When you’re playing with Rickie Fowler, nobody cares if I’m defending champion,” he joked. “So that always takes a little pressure off. It’s an honour to be the defending champion and hopefully I can keep my trophy.”
Fowler, the 2015 Scottish Open champin, covered the back nine in 31 and completed a flawless 65 with birdies on the second and ninth, where he holed from around 20 feet.
“It’s always nice to start with seven under par, I’m pleased with that,” admitted the American afterwards. “I knew with the soft conditions they were going to try to tuck some pins. It was going to be very scoreable if you drove it in the fairways and I was able to do that.
“I played very well tee-to-green and that made things a lot easier from there. It was a stress-free, simple round.
“Russell (Knox) and Paul (Casey) have been playing well and we enjoyed each other’s presence. We had a good time out there and fed off each other a bit.”
Karlberg started with four birdies, added five more before dropping his only shot of the day at the 18th as he grabbed the lead on his WGC debut.
“It was just one of those days; it was a walk in the park,” said the 2015 Italian Open champion. “I committed to a lot of shots and hit them perfectly, just as I wanted.
“With the wet conditions you just need to be aggressive, bomb to the tee and bomb to the pin, and that’s what I did today. I had great distance control. I hit great shots all day except the last hole.
“My drive there didn’t fade and I ended up in the bunker and I had a little sand behind the ball.
“Unfortunately I didn’t really catch it and ended up in the rough, short right, in the water.”
Japan’s Hideki Matsuyama and American Daniel Berger matched Knox’s 66 while Italian Francesco Molinari and American Bill Haas are alongside Casey on five-under.
Rory McIlroy, the world No 3, had to settle for a 71 as he chases the victory he feels will be necessary to have a chance of winning the Race to Dubai for the third year running.
Danny Willett, who leads the Order of Merit title contest, battled back from being five-over to card a 74 while Open champion Henrik Stenson, the other player in the Race to Dubai mix, had a 69.