The encounter will see the pair battle in one-on-one competition, with the winner taking home $9 million (£7 million) in prize money.
Woods and Mickelson have won 19 majors combined in their careers, and the special event will take place during the Thanksgiving weekend.
The contest is set to tee off at 3 p.m. (ET)/10 a.m. (GMT) and will be broadcast on pay-per-view in the United States, streaming live on B/R Live.
According to OddsShark, Woods is the 53-100 favourite to win, with Mickelson at 33-20.
There's certainly a thirst from modern sports fans to see dream clashes between the icons of different disciplines.
Boxing and MMA have travelled down this route over the years, with former greats and legends going head-to-head, but golf fans only get the chance to see such one-on-one battles during events such as the Ryder Cup.
Las Vegas will host an exhibition match for the ages, with a resurgent Woods squaring up to fellow American Mickelson.
The encounter is a winner-takes-all situation, with the purse dwarfing the cheques earned by major winners across the globe.
Woods and Mickelson exchanged tweets after the match was announced:
Woods has experienced a phenomenal comeback after beating the injury concerns that have dogged his career in recent years.
The 42-year-old is back to playing his best golf and again competing at the top of the leaderboard.
Mickelson, 48, featured with Woods for the United States at the Ryder Cup, but neither man could produce their best as Europe swept to victory in Paris.
The competition was a step too far for Woods, with fatigue playing a huge part in his disappointing performance at Le Golf National.
With the bad experience behind them, the two greats of the game will fight it out in Nevada. Most punters believe Tiger will prevail.
There's a number of side bets that will be played out on the day, with fans even able to place money on the colour of each player's shirt.
According to OddsShark, Mickelson is 3-2 to wear white, 5-2 to wear black and 4-1 to wear blue or any other colour.
Woods is 3-1 to wear red or white, 9-2 to wear black and 3-2 to wear any other colour.
The event could be a trailblazing day for golf, with the sport finding new ways to attract fresh followers.
Golf has always been a sport of grand tradition after its invention in Europe hundreds of years ago, but a modern take could see a new audience lured to courses across the world.