Kupp spun cornerback Eli Apple around, before Apple fell to the turf of the Los Angeles Memorial Coliseum.
It took linebacker A.J. Klein to finally take Kupp down 66 yards later, and only inches short of the goal line.
"It felt like a movie," Kupp said about his improbable catch-and-run. "It felt like slow motion."
Quarterback Jared Goff crossed the goal line on the ensuing snap to seal a 27-9 victory and the Rams improved to 2-0.
According to NFL Next Gen Stats, Kupp has reached a maximum speed of 16.71 miles per hour on the play and traveled a total of 85.38 yards as he zig-zagged his way down the field.
"When it comes to him, the first man never can bring him down," said Cooks, who caught three passes for 74 yards. "When you start seeing the first, second guy, you think, 'OK, we got to come up with some blocks to help him out' -- then he did the rest."
Kupp underwent reconstructive knee surgery 10 months ago after he suffered a torn ACL in a Week 10 victory over the Seattle Seahawks.
He was a limited participant in the offseason program before getting cleared to practice in training camp.
Despite appearing strong through a joint practice against the Los Angeles Chargers and two workouts against the Oakland Raiders, it remained uncertain how Kupp's surgically repaired knee would respond when the season opened.
"He looked awesome and it was incredible," Rams coach Sean McVay said Sunday. "He sure looks good, doesn't he? He looks healthy to me."
Kupp caught five passes for 120 yards against the Saints after making seven catches for 46 yards in Week 1.
In the second quarter, Goff found Kupp for a 15-yard completion over the middle. Goff went to him again in the third quarter for a 27-yard reception.
"Me and him are so much on the same page," said Goff, who overcame a slow start to pass for 283 yards and a touchdown. "At this point, we think intuitively with each other. What's the word? Telepathy?"
In two games, Kupp has 12 catches for 166 yards.
"It feels great," Kupp said, when asked about his return to the lineup. "Going through the recovery was a grind."
Despite the telepathic nature of their relationship, even Goff was a bit stunned to see Kupp's breakthrough catch-and-run.
"I was shocked," Goff said. "He's showing off some speed now."