It's a beautiful body of water and the fall environment adds to the experience. As Jeff mentioned, the people are very friendly. I'm on the Margaree all season, it's been my second home for the last 15 years. A first run might appear in mid-June, they are small in numbers but accumulate through the summer. The fish usually move into the few remaining deeper pools / pockets, the exception being high water. The early Salmon tend to be more aggressive than the fall fish. Also, the more productive pools will get crowded but if you're willing to explore lesser pools, you'll be rewarded with solitude and (possibly) fish.
For summer runs, it's most productive from the Etheridge pool down. Late summer, Fahey pool down and for a remote fall fishing experience try the Big Intervale pools. Additional fall fishing opportunities are the Middle and Baddeck rivers, which are nearby. An early season June adventure is the Cheticamp river but it's an ambitious hike to the pools.
At one time, fall fishing was exceptional but it's become very inconsistent. While local opinions vary, I find the overall numbers dwindling and that fall fishing has become....well, overrated. The past few years I've avoided Oct fishing because the fish are dark and easily stressed. But this is my personal preference. It's likely you will see fish stacked up in certain pools and ignoring everything you toss.......welcome to Atlantic Salmon fishing.
With or without Salmon on the end of my line I enjoy the experience of the Margaree, the valley and it's people. I would be happy to supply you with the names / numbers of guides, lodging or other information. One final thought, if you have time, phone and ask (local guide) about the water and fishing conditions, they can change weekly. As in > you should have been here last week.