Less than 24 hours after world number one Ana Ivanovic's shock exit, third seed and 2004 champion Kuznetsova joined the scrapheap following a 6-3, 6-7, 6-3 humbling by tenacious Slovenian Katarina Srebotnik.
American Davenport's defeat was less surprising as she came up against French 12th seed Marion Bartoli and went down 6-1, 7-6 in a blaze of double faults.
Roger Federer, Novak Djokovic, Andy Roddick and Jelena Jankovic did not have it all their way either but lived to fight another day, unlike Kuznetsova who cut a sorry figure as she trudged out after suffering her worst showing in New York for three years.
Moment of triumph
"I had chances, I was fighting, I wanted so much to win that match... (but) she played unbelievable," said 2007 runner-up Kuznetsova, who got a soaking late in the second set following a short shower burst.
After squandering two match points, Srebotnik fired down an unreturnable serve on the third and sank to her knees in her moment of triumph. It was the first time the Slovenian 28th seed reached the fourth round at the Open in 10 attempts.
The number 10 was also significant for Davenport as it has been a decade since she won her first grand slam title at Flushing Meadows. On Friday, fans may have caught their final glimpse of the 32-year-old on a singles court. Uncharacteristically her latest defeat was peppered with an alarming number of double faults.
While many Americans were eager to get home early on Friday for the start of the long Labor Day weekend, Federer, Djokovic and Jankovic appeared to be in no hurry to join the celebrations and laboured to victory.
Federer, still getting used to his place at the bottom of a draw after being deposed as world number one by Rafael Nadal last week, should have strolled into the third round as he was playing a Brazilian qualifier who had not played a tour-level match this season before arriving at Flushing Meadows.
Instead Thiago Alves ignored his status as the 137th best player in the world and gave the four-times champion the run around before Federer eventually prevailed 6-3, 7-5, 6-4.
"He did well. It was a really difficult match. I'd never heard of him before and that's what sometimes makes it difficult," Federer, aiming to become the first man since Bill Tilden in 1924 to win five in a row here, said courtside after his smooth victory.
Troubled times
In a sign of his troubled times, Federer racked up 46 unforced errors and converted only four of his 15 break points.
Roddick thrilled his home crowd by coming back from a set down and trailing in the second against young Latvian Ernests Gulbis, who was near perfect in the opening set, booming in his first serves and ripping winners from all angles.
Roddick withstood the onslaught from Gulbis to win the second-round match 3-6, 7-5, 6-2, 7-5 in a late night session during which both players celebrated birthdays as the clock struck midnight. Roddick turned 26 and 40th-ranked Gulbis left his teen-age years behind to turn 20.
Spot of bother
Djokovic too ran into a spot of bother in his opening set when he had to save two set points but took it in his stride to subdue American qualifier Robert Kendrick 7-6, 6-4, 6-4.
Drama queen Jankovic again set the pulses of her nearest and dearest racing as she struggled to steer past China's Zheng Jie.
In an error-riddled match featuring 14 breaks, Jankovic could not believe her luck when she was dragged into an 18-minute final game. After surviving seven break points, the Serbian second seed claimed a 7-5, 7-5 third-round victory.
Jankovic's potential semifinal opponent, Olympic champion Elena Dementieva, ended the run of Briton Anne Keothavong 6-3, 6-4. Next up for the Russian will be China's Li Na.
Among the men, fifth seed Nikolay Davydenko and Olympic silver medallist Fernando Gonzalez advanced to the last 32.
Spanish 15th seed Tommy Robredo ended the run of former champion Marat Safin of Russia 4-6, 7-6, 6-4, 6-0.
