Auckland - Top seed John Isner crashed out of the Auckland Classic on Wednesday while a calf injury dashed four-time champion David Ferrer's hopes of a fairytale final appearance in New Zealand.
Isner was sent packing after fellow American Taylor Fritz held his nerve in two tie-breaks to win 7-6 (7/3), 7-6 (7/5), while compatriot Tennys Sandgren brushed aside third seed Marco Cecchinato of Italy 6-3, 6-3.
Second seed Fabio Fognini narrowly avoided the same fate, with German's Peter Gojowczyk taking the match to a third-set tie-break before the Italian prevailed 6-2, 3-6, 7-6 (7/5).
The draw - already weakened by the withdrawal of defending champion Roberto Bautista Agut, Tomas Berdych and Gael Monfils - now has only two seeds remaining in Fognini and Pablo Carreno Busta of Spain.
Carreno Busta had an armchair ride into the quarter-finals when Ferrer succumbed to injury just three games into their match.
Former world number three Ferrer has retired from Grand Slams but is making a few appearances at his favourite ATP tournaments in 2019, with Auckland first on the list.
The 36-year-old looked sharp against his fellow Spaniard and they were one game apiece before Ferrer twisted his leg while hitting a cross-court forehand.
He tried to continue with strapping on his calf, managing to win a point on serve before reluctantly calling it quits.
Ferrer received a standing ovation at the tournament he described as "a second home" and said he was sorry his dream of winning a record fifth title was over.
"Of course it's disappointing but don't worry because I've had very good memories here, I'm very proud" he told the crowd.
"Remember, I won the last point," he joked before limping off centre court.
Isner, a two-time champion in Auckland, received a bye into the second round because of his seeding and looked rusty as his booming serve failed to dominate Fritz.
"It feels great. John's beat me twice before and I really wanted to get the win on him" Fritz said after downing the world number 10.
"We had a lot of close points... I like to think one of the strengths of my game is playing under pressure and handling those big moments well."
Elsewhere, Germany's Philipp Kohlschreiber defeated Ugo Humbert of France 6-4, 6-4 to set up a quarter-final against Fognini.
Britain's Cameron Norrie beat Joao Sousa of Portugal 7-6 (7/5), 6-4 and Argentinian Leonardo Meyer came from behind to down Italy's Matteo Berrettini 5-7, 7-6 (7/5), 6-3.
Hometown hope Rubin "Jose" Statham's campaign ended when the New Zealander fell to Jan-Lennard Struff of Germany 6-2, 6-1.
Results from day three of the ATP Tour' Auckland Classic tennis tournament on Wednesday (x denotes seeding):
Taylor Fritz (USA) bt John Isner (USA x1) 7-6 (7/3), 7-6 (7/5)
Cameron Norrie (GBR) bt Joao Sousa (POR) 7-6 (7/5), 6-4
Pablo Carreno Busta (ESP x4) bt David Ferrer (ESP) 1-1 (withdrew injured)
Leonardo Mayer (ARG) bt Matteo Berrettini (ITA) 5-7, 7-6 (7/5), 6-3
Tennys Sandgren (USA) bt Marco Cecchinato (ITA x3) 6-3, 6-3
Philipp Kohlschreiber (GER) bt Ugo Humbert (FRA) 6-4, 6-4
Fabio Fognini (ITA x2) bt Peter Gojowczyk (GER) 6-2, 3-6, 7-6 (7/5)
Jan-Lennard Struff (GER) bt Rubin "Jose" Statham (NZL) 6-2, 6-1