The route is best done during August (3-6 weeks), when bugs are sparse, days are long, and colors intensifying, with food drops at Anaktuvuk Pass (Post Office), Circle/Kutuk Lakes (bear barrels) and Pingo Lake (bear barrels). Bring a sat phone.
Anaktuvuk, Arrigetch, Ambler are three touchstones of the central Brooks Range from east to west, and as a packrafting trip in the Brooks Range it's hard to beat these 400 miles. The route passes through the best mountain sections, including the Doonerak region, Arrigetch Peaks and front range of Igikpak. It floats North Fork of Koyukuk to Ernie Creek, John River to Wolverine Creek, Pingaluk to Alatna, the Noatak to Lake Matcherak, and all of the Ambler River. It follows game trails and excellent creek and river bars and avoids more tussocks and brush than you'd believe.
Drive up the Dalton Highway to a little turn-off to the west, just before the pipeline road leaves the Dietrich valley bottom and just downstream of Nutirwik Creek. It's about sixty miles north of Coldfoot (you could fly to Coldfoot from Fairbanks on Arctic Air for $250). Hike up Koyuktuvuk, Trembley, Blarney Creeks and over Kinnorutin Pass to descend Amawk Creek and paddle N. Fork Koyukuk (PR 3 -- PR 4 at high water). Climb Doonerak via a scramble up its south ridge, if you like heights and broad views.
From the junction of North Fork Koyukuk and Ernie Creek there is a bit of tussocks to the Valley of the Precipices. Unbelievably, this should be one of only two tussock stretches, if you read your landscapes well en route to Ambler. Bar-hop on mature willow bars or follow well-drained tundra ridges and noses to Graylime and Anaktuvuk Creek. If you are travelling light (i.e. have a food cache in Anaktuvuk mailed to the PO there) these creeks are mostly paddleable, except for some braids on the lower Anaktuvuk, where you can pick up an ATV trail and follow to Anaktuvuk Pass, a friendly village IMO. Peggy and I took a week to Anaktuvuk in one boat in 1986; I walked from Anatuvuk to the road in a day and a half in 2006. Plan for four-five days, three days if you have Wilderness Classic experience.
The mystery spot, so named because it seems as if the water is flowing the wrong direction. Several travelers through here have commented on this optical illusion. The views are good, but the rocks to come are bad, if short -- the last ones, really.