Goals either side of half-time propelled Mayo into a fifth successive All-Ireland semi-final at Donegal's expense.
The Connacht champions always had the upperhand against opponents who looked lethargic as they struggled with a second intense game in eight days, after a draining four-match Ulster Championship campaign.
Ultimately the difficulty of their provincial route caught up with Donegal. Mayo fully exploited that and, critically, were able to control the game when they forged ahead.
They were sharper and more effective in the tackle throughout but it was the goals that broke the game.
Neil McGee and Aidan O'Shea, after his exploits against Galway and Sligo at full-forward, was always going to be a compelling battle and for much of the first half McGee had a slight upperhand, winning four of their seven direct duels.
But just as referee David Gough began looking at his watch to call the interval O'Shea struck forcefully, grabbing another perfectly aimed delivery from his imperious brother Seamus, dismissing the presence of McGee and two flankers and smashing a low shot past Paul Durcan.
Given the company he was keeping it was worth double the three goals he scored against Sligo, pushing Donegal into a 1-7 to 0-6 lead.
Donegal were dealt a further blow just after the break when McGee was forced to retire from the action.
And it got worse for them when Seamus O'Shea picked out Cillian O'Connor with another precise pass in the 37th minute, O'Connor transferring quickly to Keegan whose half-hit point attempt dipped as it went over Durcan.
As the rain began to fall it felt like the end for Donegal.
On the burst Keegan, who had opened so well with Mayo's opening two points from play, won a free and O'Connor obliged to make it an eight-point lead.
Mayo locked it down impressively after that without ever really stretching Donegal.
As a sign of how weary Donegal were the normally assured Karl Lacey passed
across his own goals inviting Kevin McLoughlin to nip in for a second point.
Keith Higgins was immense in defence, repeatedly clearing danger with a quick burst of acceleration.
Murphy was always Donegal's biggest threat. He scored eight points, three from play and was an effective target at full-forward for much of the game.
But Mayo never left Ger Cafferkey isolated on him and at time he had the protection of Barry Moran planted in front of him.
As Donegal chased they were forced out of the strong defensive structure they thrive on and Mayo were able to pick holes.
Donegal got to within six points at one stage near the end but Mayo kicked on with late points from Andy Moran and Jason Doherty, another impressive performer with three points.
At the very end Mayo substitute Kevin Keane, only on the field a minute, was red-carded for throwing a punch at Murphy.
The defeat will cast doubts over the future of some of Donegal's veterans. Christy Toye, who was withdrawn at half-time, and Colm McFadden especially while the futures of Durcan and Thompson are also up in the air.
Scorers - Mayo: L Keegan 1-2, C O'Connor (3fs), J Doherty 0-3 each, A O'Shea 1-0, K McLoughlin 0-2, A Freeman, A Moran, K Higgins 0-1 each.
Donegal: M Murphy 0-8 (5fs), A Thompson, L McLoone, C Toye all 0-1 each.
Mayo: D Clarke; G Cafferkey, T Cunniffe, K Higgins; L Keegan, D Vaughan, C Boyle; S O'Shea, B Moran; D O'Connor, T Parsons, J Doherty; K McLoughlin, A O'Shea, C O'Connor. Subs: C Barrett for Cunniffe (33), R Hennelly for Clarke (ht), P Durcan for Vaughan BC (54), A Moran for Moran (temp 60), A Freeman for S O'Shea (65), K Keane for Cafferkey (70).
Donegal: P Durcan; E McGee, N McGee, P McGrath; M McHugh, K Lacey, F McGlynn; N Gallagher, H McFadden; C Toye, O MacNiallias, R McHugh; C McFadden, M Murphy, P McBrearty. Subs: M McElhinney for Toye (ht) A Thompson for N McGee (38), L McLoone for MacNiallais (39).
Referee: David Gough (Meath)