Not even a second-half appearance from Ciaran McDonald could keep Mayo's All-Ireland hopes alive at Celtic Park, as Derry claimed their second big scalp in the space of a week.
McDonald ended his ten-month injury-enforced absence from the Mayo side but Derry, with Collie Devlin and Enda Muldoon chipping in with goals, romped through to the third round of the qualifiers.
Mayo, last year's beaten All-Ireland finalists,were 0-04 to 0-00 behind before a 16th-minute handling error from Derry 'keeper Barry Gillis allowed Barry Moran in for a goal to open the westerners' account.
Derry led 0-08 to 1-03 at half-time and top-scorer Paddy Bradley, who finished with five points, guided them home to a well-merited win.
Conquerors of Armagh last Sunday, Derry finished this game 'brimming with confidence', in the words of their talisman Bradley, and no team will want to face them in the next round - especially at Celtic Park.
Paddy Crozier's men were certainly on a mission today and they played at full tilt right from the off. They left Mayo in their wake as they moved 0-04 to 0-00 ahead, with the promise of more to come.
Former All-Star forward Muldoon, now recovered from his recent bout of 'flu, was a late inclusion in the Oak Leaf line-up, with Mark Lynch making way.
A foul on Muldoon led to Bradley opening his account in the 15th-minute, after Conleith Gilligan, Barry McGoldrick and James Conway, who profited from a peach of a pass from Gilligan, had all angled over points.
Bradley's score had Derry four to the good but they were stunned just seconds later when a ball played in towards the Derry square by David Heaney was fumbled by Gillis and big full-forward Moran was on hand to tap home the loose ball for his second goal in as many matches.
A Conor Mortimer free brought the sides level before Derry weathered the brief storm with scores from Gilligan and the very effective Devlin.
Moran, all 6ft 5in of him, was proving hard to handle and the Castlebar giant stroked over two points off his left and his right to display his undoubted talent. His second opportunity may have led to a goal as he blazed an effort just over Gillis' crossbar.
But a late Bradley point sent Derry in at the break with a 0-08 to 1-03 advantage and with Mayo's forward unit, bar Moran, largely off-colour, Crozier's men were well worth their lead.
Mayo did level at 0-08 to 1-05 as they made a solid start to the second half. Substitute Aidan Kilcoyne, on for the disappointing Alan Dillon, and teenager Pierce Hanley dinked over the half's opening two points.
John O'Mahony's outfit looked to be mounting a comeback but Derry, with Muldoon's switch to midfield proving a masterstroke, quickly shut the door as the visitors' scores dried up and those two crucial goals arrived.
Subsitute Mark Lynch almost found the Mayo net in the early stages but he dragged his shot to the left and wide. Muldoon then used all of his height to claim a high ball, pick out Conway and he sought out Devlin who cleverly fisted to the net in the 58th-minute to send Derry three points clear again.
Mayo threw McDonald, who has battled back from a long-term back injury, into the fray but the former captain could do little as the Connacht side's shooting boots let them down - they finished with 14 wides, double Derry's total.
Bradley and substitute Raymond Wilkinson tagged on points for a 1-10 to 1-06 scoreline. Two more points - the first a fabulous free - brought Bradley's tally to five before Muldoon rubbed salt into Mayo's wounds by grabbing a 67th-minute goal - a brilliant lobbed finish from 20 metres out which arced over the head of stranded goalkeeper David Clarke.
Mayo only have themselves to blame for letting Derry canter home. The visitors' sixth and final point came from Andy Moran in the 54th-minute, putting just two points between the sides, but Derry's strong finish left the result in little doubt.
Derry: B Gillis; M McGoldrick, K McCloy, G O'Kane; L Hinphey, SM Lockhart, F McEldowney; F Doherty, J Conway (0-01); B McGoldrick (0-01), P Murphy, E Muldoon (1-01); C Devlin (1-01), Paddy Bradley (0-05, 0-02f), C Gilligan (0-03, 0-02f).
Subs used: M Lynch for McGoldrick (29 mins), R Wilkinson (0-01) for Murphy (56), Patsy Bradley for Conway (60), P O'Hea for Hinphey (67), G Donaghy for Gilligan (70).
Mayo: D Clarke; T Cunniffe, L O'Malley, T Howley; D Heaney, D Kilkullen, T Mortimer; D Brady, P Harte; BJ Padden, P Hanley (0-01), A Dillon; C Mortimer (0-01, 0-01f), B Moran (1-02), A Moran (0-01).
Subs used: A Kilcoyne (0-01) for Dillon (half-time), A Campbell for Kilcoyne (53 mins), C McDonald for Campbell (59), K O'Neill for Padden (60).
Referee: David Coldrick (Meath).