First up on centre court in the night session, the world number 11 took out the first set tiebreak 10-8.
Isner, who stands at over two metres tall, was forced to rely heavily on his serve, with Querrey hitting the bulk of the winners on the rallies.
On the outside courts Kiwi pair Finn Tearney and Wesley Whitehouse are a set down in their doubles showdown with the USA's Donald Young and Nicholas Monroe.
5.33pm
American Jack Sock wowed the crowds at the ASB Tennis Centre with his impressive court craft and big forehand on his way to a 6-2 6-4 win over his good friend and doubles partner Vasek Pospisil of Canada this afternoon.
Sock will now meet big-serving South African and fourth seed Kevin Anderson in tomorrow's quarterfinals.
Others to book their place in the quarterfinals this afternoon were Spaniard Roberto Bautista Agut and Lukas Rosol of the Czech Republic who posted identical 6-4 7-6 scorelines in their respective matches.
Bautista Agut overcame the USA's Donald Young, while Rosol toppled popular Frenchman Benoit Paire.
3.42pm
Top seed David Ferrer has wasted little time in booking his place in the quarterfinals, ousting qualifier Matthew Barton in straight sets in today's second round match-up.
Ferrer, who accepted a late wildcard for the tournament after a shock first round exit in Doha last week, was too crafty, too quick and too experienced for the young Australian, recording a 6-2 6-4 win.
The world No. 7, who is chasing a record fifth title in Auckland, was in action for the first time at the ASB Tennis Centre today after being handed a first round bye alongside his fellow top four seeds.
The Spaniard will face the winner of this afternoon's match between Frenchman Benoit Paire and Lukas Rosol (CZE) in tomorrow's quarterfinals.
2.20pm
The world No12 Kevin Anderson has progressed to the second round, after a 7-6 (8) 7-6 (5) win over Robin Haase. This match was supposed to be the entree to the bigger matches on later today but the Dutch qualifier pushed the fourth seed much harder than expected. Haase broke back late in the second set to take the set to a tiebreak, then took a 4-1 lead in the breaker. But Anderson showed his class to win
six of the next seven points.
1:30pm
Kevin Anderson has taken the first set 7-6 (10-8) against Robin Haase. It's the kind of battle most expected, with two big servers going head to head.
The tiebreak was a beauty, with Haase coming up with one of the best retrievals of the match midway through the breaker. However, the Dutchman let himself down on set point with a double fault to gift Anderson the set.
12:30:
A bumper day ahead at the ASB Classic and the weather gods are smiling - it's a sunny bright day in Auckland. All four of the top seeds (Kevin Anderson, David Ferrer, John Isner and Jo-Wilfried Tsonga) are in action today, as well as other big names like Jack Sock, Fabio Fognini, Benoit Paire and Sam Querrey.
There is also local interest, with Michael Venus (alongside Croatian Mate Pavic) in the doubles as well as Finn Tearney and Wesley Whitehouse.
Anderson is first up on centre court, against Dutch qualifier Robin Haase. The South African won their encounter, a 6-3 3-6 6-2 6-2 victory in the Davis Cup.