The Swiss, who is not guaranteed to end the year on top of the rankings, will also face Britain's Andy Murray and Spain's Fernando Verdasco in Group A at the eye-catching O2 Centre alongside the River Thames when play starts on Sunday.
Rafael Nadal, who missed last year's finals in Shanghai, appears to have the easier draw as he tries to topple Federer from the world number one spot.
The Spaniard, who beat Federer in the Australian Open final, will play Serbia's world number three Novak Djokovic, Russian Nikolay Davydenko and Swede Robin Soderling, who ended Nadal's reign at the French Open this year.
Soderling, beaten in the French Open final by Federer, replaced American Andy Roddick, who withdrew from the event on Tuesday with a knee injury.
Argentina's Del Potro stunned Federer at Flushing Meadow in September, preventing the Swiss winning the title for a sixth consecutive year, and their meeting will be an intriguing contest, as will Nadal's re-match with Soderling.
One million pounds is up for grabs if a player wins the title in London undefeated -- more than the 850,000 pounds Federer collected for winning Wimbledon this year.
London is beginning a five-year stint as host of the ATP Tour finals, with more than 255,000 tickets already sold for the eight-day event.
Qureshi beats Federer in Basel doubles
Federer eases into home-town quarter-finals
Somdev drops to 124, Amritraj gains 19 places
First look: Del Potro atop Empire State Building
Spotted: Saina Nehwal at Copenhagen