All but six of the remaining 100 players will tee up for the US$8million event in Norton, Massachusetts, with several set to be scurrying to qualify for the BMW Championship.
The top 70 players on the points list following this week's event will make it to the third play-off tournament.
Reigning FedEx Cup champion Henrik Stenson returns to the scene of his two-stroke success in 2013, when he matched the course record of 22 under.
This year, the Swede needs a solid performance to ensure himself of progression to the BMW, as he sits 66th in the rankings.
The PGA Tour website projects Stenson needs to finish inside the top 56 to ensure his Cup defence goes on.
The Barclays winner Hunter Mahan has assumed the Cup lead on 3,276 points, with Northern Ireland's Rory McIlroy (2,810) in second.
McIlroy's run of three straight tournament wins - including The Open Championship and US PGA Championship - came to an end thanks to Mahan, but England's Paul Casey conceded that the world number one is still the man to beat.
"When Rory is on, it's not a contest," Casey, who will miss the event for personal reasons, said in quotes reported by the New York Times.
"Rory's swing is like a bullwhip. When he times it, it's the best you're going to see. I've never seen a golf ball hit like that."
The injured Jason Dufner is also among the absentees, with him and Casey therefore ending their respective FedEx Cup bids.
Also out of the event in Boston is Graeme McDowell, the Northern Irishman taking time off after wife Kristin gave birth to the couple's first child on Monday.
McDowell sits 40th in the points list, ensuring he will be safely through to the BMW.
Other players in danger of missing out on the next tournament are Shawn Stefani, Jason Bohn, KJ Choi and Scott Brown - the players occupying spots 67-70.
Big names currently outside the top 70 trying to get into it include Brandt Snedeker (71st), Luke Donald (80th), and Vijay Singh (95th).