Midfielder Joe Keith set Leyton Orient on their way to victory with a goal inside two minutes of his debut.
The former Colchester playmaker stabbed home after good work by Lee Steele and Gary Alexander and a defensive mix up.
Macclesfield served notice when John Miles hit the bar before Paul Harsley pounced to level and Alan Russell tested Orient goalkeeper Glyn Garner.
Home substitute Efe Echanomi wasted two chances before sealing the win when he capitalised on another defensive lapse.
Leyton Orient: Garner, Barnard, Lockwood (Carlisle 68), Zakuani, Mackie, Tudor (Easton 83), Simpson, McMahon, Keith, Alexander, Steele (Echanomi 72).
Subs Not Used: Dolan, Morris.
Booked: Echanomi.
Goals: Keith 2, Echanomi 90.
Macclesfield: Fettis, Bailey, Morley, Swailes, Sandwith, Miles, McIntyre (MacKenzie 53), Harsley, Bullock, Russell, Beresford.
Subs Not Used: Townson, Whitaker, Barras, Deasy.
Goals: Harsley 57.
Att: 3,600
Ref: M Thorpe (Suffolk).