The 31-year-old, who is bidding to become just the second player after Tiger Woods to successfully defend a WGC title, had moved from six-under overnight to 10-under with five holes to play at Sheshen International.
Knox, who won with a 20-under total on the same course 12 months ago, birdied the second before dropping his first shot of the event with a 5 at the third.
In breezy conditions, he then picked up three birdies in four holes from the fifth to be out in 33 before continuing his excellent title defence with a 2 at the 12th.
The clubhouse target had been set by Japan’s Hideki Matsuyama after he backed up a first-day 66 with a 65 to sit on 13-under.
World No 3 Rory McIroy jumped up the leaderboard after a 66 to sit seven-under.
Colin Montgomerie sets out in fourth spot as the inaugural Charles Schwab Cup Play-Offs get underway in California today.
The Scot jumped up the rankings after winning in Canada a month ago but has his work cut out to catch runaway leader Bernhard Langer in the three end-of-season events.
Montgomerie is in the second last group for the opening round of the Power Shares QQQ Championship in Thousand Oaks.
Senior Open champion Paul Broadhurst also has two Americans - Jay Haas and Brandt Jobe - for company.
Langer, who won the Charles Schwab Cup for the second season in a row and third time in total last year, is out with his two nearest challengers, Joe Durant and Miguel Angel Jimenez.
Irishman Seamus Power opened with a flawless seven-under-par 65 to sit just two shots behind leader Kevin Streelman after the opening round of the PGA Tour’s Sanderson Farms Championship in Mississippi.
Streelaman signed for 10 birdies as he set a hot pace in Jackson, where English duo Greg Owen and Ian Poulter carded 67 and 70 respectively.
Catriona Matthew is set for a rare missed cut on the LPGA Tour despite a big second-round improvement in the Sime Darby LPGA Malaysia.
The Scot, who’d opened with a 75, was one-over after 17 holes in Kuala Lumpur, where Amy Yang had set the pace with a 63.
Vikki Laing’s hopes of making it to the weekend in the LET’S Sanya Ladies Open were dashed by a second-round 78 in China this morning.
The Scot had opened with a 73 but was set to make an early exit along with compatriot Carly Booth (77-76).
With Laura Murray and Pamela Pretswell still playing their second rounds, former Ladies Scottish Open champion Gwladys Nocera secured a share of the clubhouse lead on six-under.
Long-serving Edzell pro Alistaur Webster and Carnoustie amateur Scott Robertson shot matching one-over-par 74s to share top spot in the Midland Golfers’ Alliance at Drumoig.