The Uzbek world number 43 needed just one hour and 13 minutes to dispatch the Turkish qualifier at the ATP 250 hard-court event, securing a 6-4 7-5 win.
IIlhan displayed admirable resistance in the first set, holding firm until Istomin finally secured the crucial break in the 10th game to take command of the match.
However, Ilhan's resistance did not wane despite that setback, but the world number 188 was undone in the 12th game of the second as Istomin snatched the only break of the set to ensure his place in the last 16.
Adrian Mannarino won one of the three all-French clashes of the day in Montpellier, overcoming compatriot Vincent Millot 6-4 6-4.
World number 72 Mannarino produced an assured performance to qualify for the second round, winning 88 per cent of points on his first serve.
There was no such fortune for Michael Llodra, who succumbed to a 6-4 7-6 (7-4) defeat to qualifier Marc Gicquel.
Gicquel ensured success over his fellow Frenchman in a second set tie-break, recovering quickly after failing to serve for the match at 6-5.
Qualifier Albano Olivetti triumphed in the other contest between two locals as he came back from a set down to beat Kenny De Schepper 4-6 7-6 (7-2) 6-4 in one hour and 52 minutes.
Elsewhere France's Pierre-Hugues Herbert beat Andres Artunedo Martinavarr 6-4 6-3.