After an opening a one-over-par 71, the Northern Irishman shot a second-round 68 to lie on one under par.
That was two shots outside the halfway cut-off of 137.
McDowell had been 131st in the standings with only the top 125 going forward to the play-offs after this tournament.
Shane Lowry, needing to finish in the top 10 to progress, jumped up to joint ninth after a splendid 64 on Friday, adding to his first-round 67.
Lowry, from County Offaly, had four birdies on the back nine and sits four shots behind leaders Webb Simpson and Ryan Armour who are on 13 under, one shot ahead of Henrik Stenson.
Seamus Power just made the cut on three under par after a second-round 70.
The Waterford man was in 123rd spot going into this week so has kept alive his chances of making the play-offs.
Padraig Harrington carded a second-round 68 and is on six under par.
The three-time major winner was 199th in the FedEx standings and only a win or second place this week would see him moving up to the top 125.
However, the 45-year-old from Dublin has a medical exemption following back surgery would allow him to play in nine tournaments next year.
The play-offs will begin with the top 125 competing at the Northern Trust Open.
The leading 100 will then go on to the Dell Technologies Championship with the top 70 in action at the BMW Championship before the leading 30 compete in the concluding Tour Championship in Atlanta.
Graeme McDowell's hopes of reaching the FedEx Cup play-offs ended as he missed the cut at the Wyndham Championship in Greensboro, North Carolina.