Woods is the only returning player from last year's event, which was won by Greg Norman. Norman won't defend his title because of a prior commitment.
The 20th Skins Game will be played on November 30 and December 1 at the Landmark Golf Club.
Mark O'Meara and Fred Couples will join Woods and Mickelson in this year's field.
This will be Woods' fourth appearance in the Skins Game, while Mickelson will be playing for the first time.
Couples will be making his ninth Skins Game appearance. He won the title in 1995, '96 and '99.
O'Meara previously played three straight years from 1997-99.
Each of the first six holes will be worth $25,000. Holes 7 through 12 are worth $50,000 and holes 13 through 17 will each be worth $70,000. The 18th hole will be worth $200,000.
The four players have agreed to donate 20 percent of their winnings to charity.