The O's had made a perfect start when Joe Keith stabbed them ahead after 64 seconds - but Macclesfield came back into the game in the second half and Paul Harsley levelled on 57 minutes as the visitors looked as if they had salvaged a point.
In a dramatic opening to the game, Lee Steele swung over a cross from the right, skipper Gary Alexander headed down and Keith, making his Orient debut, gleefully netted from close range.
Orient continued to dominate the first half, as Alexander and midfield man Michael Simpson had shots blocked, but it was the visitors who almost levelled when an error by Simpson let in Allan Russell and he fed John Miles who thundered a an effort against the bar from 16 yards.
After the interval, Macclesfield, who made the play-offs last season, hit back as Orient's game fell apart.
Orient keeper Glyn Garner did well to block an effort from Miles, but the rebound fell to Harsley who fired an equaliser into the net on 57 minutes from 18 yards.
Russell, who almost joined Orient in the summer, had a couple of chances to win the game for the visitors, before the hosts regained control of the final 15 minutes.
Echanomi. on for Steele, fired just wide after he had only been on the pitch for four minutes.
As Orient cranked up the tempo, defender John Mackie saw a header bounce over the bar and then Echanomi wasted a couple of good opportunities.
But then, in stoppage time, Orient finally grabbed the winner when defender Danny Swailes decided to play a back pass to goalkeeper Alan Fettis, but Echanomi reacted quickly and intercepted the ball before rounding the keeper and tapping it into the net.