Lorenzi, 36, has a good record in New York having taken a set off Andy Murray in the third round in 2016 before reaching round four last year, but this still looked a good draw for Beverley’s Edmund, now a solid top-20 player and the 16th seed.
The British No 1 has not shown the form he would have liked on the North American hard courts, winning only three matches in four tournaments, but had the better of three straight breaks of serve to start the match before taking the first set.
But, gradually, Lorenzi and the punishingly hot and humid conditions began to get the better of Edmund. He was broken to lose the second set and the same thing happened in the third, this time from 40-0.
By now, cramp had started to set in and Edmund called the trainer for some salt tablets. He was struggling to move, though, hopping around on the baseline as his calves tightened.
Lorenzi was not about to let him off the hook and Edmund did not win a game until 5-0 in the fourth set as he suffered a first-round loss at a slam for the first time since Wimbledon 2016.
Edmund revealed he is still feeling the effects of a viral-type illness that he was struck down by after Wimbledon, which left him less able to handle the conditions.
He said: “Physically I need to get better. It’s an indication of where I’m at.
“For sure I’m disappointed I’m like this but I’ve just got to get better. It’s nothing new to me. It’s a shame it ended like it did because it’s pretty horrible.”
Elsewhere, Heather Watson lost in the first round for the eighth successive year, going down 6-1 3-6 6-3 to Russia’s Ekaterina Makarova.
Watson won her first senior matches at Flushing Meadows to come through qualifying but was unable to follow that up with a first main-draw win.
It was a tough draw against the experienced Makarova, who always seems to bring her best in grand slams. Watson had not won a set in round one here since 2013 and showed good fighting spirit to recover from 1-3 to push the match into a deciding set.
But Makarova halted the British player’s momentum and served out the victory.