McLaughlin had set the early running in the final practice session before qualifying with a 1m16.296s, and eventually topped the times with a 1m15.460s lap to pip team-mate Josef Newgarden by 0.294s as Will Power claimed third.
After an early red flag, caused by Rinus VeeKay understeering into a wall at the cost of a nosewing on his Ed Carpenter Racing machine, Graham Rahal and Colton Herta did the same but without needing to be recovered by the safety team.
As McLaughlin headed the times into the final 30 minutes of the session, Newgarden was displaced for second by Felix Rosenqvist in the Arrow McLaren SP.
Andretti Autosport driver Romain Grosjean shaved McLaughlin’s time to move up to the top of the times before Rahal improved to take third from Rosenqvist.
Power then went quickest as the first driver in the session to dip into the 1m15s bracket, with Rosenqvist moving into second and six-time IndyCar champion Scott Dixon’s Chip Ganassi Racing taking third.
The trio were then demoted by Newgarden lapping 0.086s faster than Power, before McLaughlin went quickest moments later.
Grosjean's team-mate Alexander Rossi, who lost a lot of time during opening practice on Friday to a brake issue, moved up to fourth ahead of the man who will replace the future McLaren driver at Andretti Autosport next year, AJ Foyt Racing's Kyle Kirkwood.
Paretta Autosport’s Simona De Silvestro looked very impressive in her third outing of the year, just 0.4s behind her technical team-mates at ECR, VeeKay and Conor Daly, although the trio finished the session outside the top 20.
Qualifying begins at 3:30pm local time.