The Spaniard will contest January's Daytona 24 Hours race, as he continues his bid to complete motorsport's fabled "Triple Crown."
Alonso, a two-time world champion, will drive for the United Autosport team with the race taking place during F1's off-season.
United Autosports is owned by Zak Brown, team principal of the McLaren F1 team with which Alonso recently signed a new contract.
"What an exciting and interesting project," Alonso said in a statement. "The Daytona 24 Hours is the most iconic US endurance race and one of the world's great races. Everyone knows it."
The 36-year-old won plenty of fans in the US after an admirable performance in May's Indy 500, when he was forced to withdraw with just 21 laps remaining due to an engine failure.
Alonso has made no secret of his ambition to complete a famous trio of race wins by adding victories in the Indy 500 and the 24 Hours of Le Mans to his two Monaco Grand Prix triumphs.
"It's not part of the 'Triple Crown' but, as I have always said, my aim is to be a complete driver and this experience will help me in the preparation for any other endurance race I might take part in," he added.
The only driver to have achieved the feat is Graham Hill, the Briton who completed the set by winning Le Mans in 1972.
Alonso's tilt at Daytona is seen as him stepping up his preparation for a future drive at Le Mans.
"As I said many times, the 'Triple Crown' is the main thing," Alonso said at last weekend's US Grand Prix, where his frustration F1 season continued with a seventh retirement.
"I know that the Indy 500 was a nice thing and I felt very competitive, but it was a big challenge that I took from zero, with no testing and no similar racing experience before the Indy 500 at any other oval, it was a big challenge.
"I was competitive and it felt good but if I want to prepare for Le Mans maybe there are other possibilities to prepare Le Mans a little bit better [than I did for] the Indy 500."
The Daytona 24 Hours takes place at Daytona International Speedway and takes in parts of the NASCAR oval.
"After the great time I had during the month of May for the Indy 500 I am looking forward to taking part in another legendary race that will bring back all those amazing sensations that US fans gave me."
Brown added: "I'm thrilled we have managed to put a deal together to get Fernando in the car at Daytona.
"Although he hasn't driven an LMP2 car before I'm confident he will pick it up quickly. He's one of the best drivers around so it will be great to have him as part of the team."