Uzbekistan's Istomin, the sixth seed at the ATP 250 event, was ousted by Slovakia's Lukas Lacko 5-7 6-1 6-4 at the hard-court tournament.
Istomin was broken at the first time of asking as Lacko opened up a 2-0 lead, however the Slovak dropped serve three times for the set as the world number 41 took the first.
Lacko opened up a 2-0 lead in the second set also, however he went on to consolidate and opened up a 5-0, double-break buffer before holding to love to send the match to a decider.
Istomin's trend of starting sets slowly continued, as he was broken to love to start the third, and Lacko maintained his lead until the eighth game - when Istomin squared the set at 4-4 as he broke to 30.
However, as quickly as Istomin was back in the contest, he was out of it again, as Lacko broke straight back before defying the Uzbek a break-point chance in the 10th game to serve out the match.
Lacko will face American Jack Sock in the quarter-finals, after the rising star continued his stellar form with a 6-4 6-2 dismissal of qualifier Michael Venus of New Zealand.
Ninth seed Querrey bowed out on home soil to Israel's Dudi Sela, who posted a convincing 6-2 6-4 victory.
Sela's next assignment is Canadian fourth seed Vasek Pospisil, who dismissed Ukrainian qualifier Illya Marchenko 7-5 6-3.
In the day's lone first-round affair, Taipei's seventh seed Lu Yen-Hsun downed American lucky loser Alex Kuznetsov 6-4 6-4.