The sport has led a nomadic existence over the years in the States as it has struggled to capture the imagination of an American public.
Riverside, Sebring, Watkins Glen, Dallas, Detroit, Las Vegas, Long Beach, Phoenix and Indianapolis - the latter most recently in 2007 - have all tried and failed at some stage to showcase F1.
Now, deep in the heart of an area where NASCAR has long reigned, F1 has its own purpose-built facility - the multi-million pound Circuit of The Americas just outside Texas' capital city, Austin.
Hamilton, the last winner of a F1 race in the US five years ago in his debut year with McLaren, is confident COTA has what it takes to finally win over the sceptical Americans.
"I have to admit, I'm absolutely made-up that we're going back to the States," said Hamilton.
"It's a fantastic country and a place where our sport truly deserves to be.
"I think the Circuit Of The Americas looks like it could also be the place modern Formula One finally calls home.
"I've only driven it on the computer and in the simulator, but I think it's going to be a track that drivers enjoy, which produces some great, close racing, and which fans will quickly love.
"This is a new circuit, a new challenge and a new opportunity - I'm definitely looking to be the first grand prix winner at the Circuit Of The Americas."
Although another track designed by Hermann Tilke, who has not always produced venues conducive to spectacular racing over the seasons, it boasts a remarkable 41-metre elevation change, with its peak the apex of turn one destined to become a signature corner in F1.
Beyond that, Tilke has taken elements of some of the sport's best-loved circuits and pieced them together jigsaw-style.
Whether Tilke has produced a masterpiece, the drivers will know come the first few laps of practice on Friday.
On paper at least, the initial impressions are positive as Hamilton's team-mate Jenson Button said: "It looks to have a little bit of everything.
"The plan-view certainly looks familiar; you can see elements of the Maggotts/Becketts complex from Silverstone; there's a reverse of Istanbul Park's Turn Eight; and I can even see a bit of the Hockenheim infield, too.
"Whether those elements will blend together to make a satisfying whole remains to be seen.
"But there are a couple of long straights into tight corners, which should at least open up the possibility of overtaking.
"Overall, I think we're in for a fantastic weekend. I really cannot wait to get out to Austin and see the city, the people and the track.
"I think it's going to be brilliant."