The second seeded Austrian came from behind to beat German fifth seed Alexander Zverev 2-6 4-6 6-4 6-3 7-6(6) to win the US Open on Monday (NZ time).
Thiem became the first Austrian to claim a singles title at Flushing Meadows, albeit in unique circumstances as no fans were present at the hardcourt major due to the Covid-19 pandemic.
The triumph comes after the 27-year-old had come up one short of a major title on three previous occasions.
Thiem was the beaten finalist in this year's Australian Open and at the French Open in 2018 and 2019.
The Austrian world number three started as favourite but appeared to have blown his golden chance as he fell two sets behind.
Thiem, who had dropped only one set en route to the final, looked stifled by nerves early on but gradually broke the shackles to hit back from a break down to take the third.
Zverev faltered on serve at 3-4 in a high-quality fourth set allowing Thiem to take the contest to a decider.
A limping Thiem trailed 5-3 in a high-quality decider but summoned some incredible baseline winners to take it into a nerve-jangling tiebreak.
An astonishing climax saw Thiem squander two match points from 6-4 but when a third opportunity came Zverev fired wide after four hours and two minutes.