Matsuyama, the 2012 Masters champion, put together an eagle and five birdies as he raced clear at TPC Southwind in steamy Memphis on Saturday, reaching 17-under 193.
He left Nick Dunlap (66) a distant second entering the final round with Viktor Hovland (66) a shot further back, while world No.1 Scottie Scheffler lost ground with a 69 to be tied fourth with Sam Burns (70).
Matsuyama is bidding to claim a first FedEx Cup playoff event title.
But this postseason opener is all about moving on. The top 50 in the points standings advance to the BMW Championship next week outside Denver and will be assured of getting into all the $US20 million signature events next year.
Of the three Australians in the field, Jason Day is sitting pretty after his flawless 65 with six birdies left him tied 16th on the leaderboard at six under - projected to move up to 22nd on the standings.
Adam Scott was also going in the right direction. After starting the tournament at 55th he improved his projected finish to 45th after he shot a 68 to be tied 25th in the tournament at four under.
But Min Woo Lee remains well outside the top 50. He shot a 70 to be tied 39th at two under and projected to finish 63rd in the standings.
Jordan Spieth's season effectively ended when he made two double bogeys in his round of 74, leaving him in 69th place against a 70-man field.
Will Zalatoris came into the postseason at No.49 and shot 67 on Saturday. He was tied for sixth and all but assured of staying well inside the top 50.
