It was the sixth time McLaughlin-Levrone had broken the world record, lowering her previous mark of 50.65 set at the U.S. trials in June.
Lyles, who had been bidding to complete a 100m-200m double in Paris, was taken off the track in a wheelchair following the race, won by Botswana's Letsile Tebogo.
The 26-year-old, who had claimed virtually every other title in an utterly dominant half decade including three world championship gold medals, clocked 12.99 seconds.
A tense game ended all square at 1-1, with fourth-quarter goals in quick succession from Dutch captain Thierry Brinkman and Germany's Thies Prinz.
Nadeem threw an Olympic record of 92.97 metres for victory, India's defending champion Neeraj Chopra taking silver with 89.45. Grenada's Anderson Peters claimed bronze with 88.54m.
Marathon swimming is set to get underway amid concerns over water pollution in the river Seine.
There will be 21 medals up for grabs with the bulk of them being given out in athletics.
"The last hurrah, I'm done. I've always said I want to retire a champion, that's it," Harrington told Irish national broadcaster RTE.
Alfred is seeking to emulate Jamaica's Elaine Thompson-Herah, who did the 100m-200m double at the Rio 2016 Games and at the Covid-delayed Tokyo Olympics.
"The Olympic flame that we are lighting today symbolises this hope for a better future," said International Olympic Committee President Thomas Bach.