Spanish summer signing Kike, on target in the opening-day win against Birmingham, was one of six changes made by Boro as he started on the bench, but the Sky Bet Championship side were still far too strong for their League One opponents.
Boro could have taken an early lead when Jonathan Woodgate met Adam Reach’s corner, but headed over from six yards.
Grant Leadbitter also went close before they made their dominance count on the half-hour mark, with Luke Williams taking possession 30 yards from goal and hammering a superb shot into the top corner.
Boro’s lead was doubled in the 48th minute as Reach crossed from the left and Leadbitter calmly slotted past Oldham goalkeeper Paul Rachubka from 14 yards.
Spanish substitute Kike, who had only just come off the bench, made it 3-0 after an hour when he showed neat control before angling a pin-point 10-yard drive inside the far post.
The dangerous Kike also lobbed over the crossbar, while Oldham failed to muster a shot on target.