Kaia Kanepi defeated Halep 6-2, 6-4 on Monday in the first round in NY.
The French Open champion arrived at Flushing Meadows as one of the hot favourites and declared herself free of pressure after breaking her grand slam duck at Roland Garros.
Halep simply was overwhelmed by the power-based game of 44th-ranked Kaia Kanepi of Estonia 6-2, 6-4 in a match that was stunningly lopsided and lasted all of 76 minutes.
The 33-year-old was a quarterfinalist in NY last year. The current match wins leader on tour (46-8), Halep also led the way for hardcourt wins (28-4) but Kanepi, a quarterfinalist previous year as a qualifier, claimed her first win over a Top 20 opponent since 2015 Madrid.
No.7 seed Elina Svitolina powered into the second round of the US Open thanks to a 6-3, 1-6, 6-0 victory over Sachia Vickery who broke in the very first game before Svitolina claimed five straight games.
Kanepi advanced to 19-10 in her career at the U.S. Open on Monday.
Seeding aside, the last world No. 1 to win the U.S. Open was Serena Williams in 2014. She struggled throughout Monday's match with Kanepi and coughed up 28 unforced errors.
"Staying aggressive", Kanepi said, "all the time".
The 14,061-seat stadium became the second arena at the Billie Jean King National Tennis Centre to boast a retractable roof after a $600million (£465m) rennovation - and it may well boast the biggest upset of the 2018 event already as Halep was blown away on the first day of the final Grand Slam of the year.
Eventually, Halep got going a bit, taking advantage of Kanepi's mistakes to break back twice and get to 4-all in that set.
In addition, defending champions Rafael Nadal and Sloane Stephens were slated to play.