A late header from Michail Antonio secured a 1-0 win against Bournemouth.
As the curtain was prepared to come down on the Olympics in Rio, the venue that memorably hosted the 2012 Games was again festooned with flags and banners to mark its new incarnation as a top-flight English football ground.
But the home supporters endured a nervous wait for the celebrations to begin with Slaven Bilic's side looking hesitant in the absence of injured forwards Andre Ayew, Andy Carroll and Dimitri Payet, only breaking through in the 85th minute.
It was a finely crafted goal, though, as Antonio rose at the far post to head in from close range after a beautiful flighted cross from the left by Turkish international Gokhan Tore.
The breakthrough in part stemmed from the space created by the dismissal of Bournemouth's influential midfielder Harry Arter seven minutes earlier for a second bookable offence after bringing down Cheikhou Kouyate.
That seemed to unsettle the visitors, who had been well marshalled by Steve Cook in defence.
Bilic was delighted with the win, which ended any doubts about the wisdom of West Ham's move away from Upton Park.
"The lads were brilliant," he said. "It wasn't a good game but I didn't expect to play like Brazil. I didn't want to stay on zero points, even after just two games, because people start to ask questions. Is it a proper home? It is like a snowball."
The margin of victory would have been more convincing had West Ham substitute Jonathan Calleri, who has just finished playing for Argentina at the Rio Olympics, not wastefully shot wide after being sent free on goal in added time.
