The Red Hands trailed by nine points at one stage to a Derry side which led 2-4 to 1-5 at the break, with goals from Benny Heron and Ryan Bell.
Patrick Quinn scored Tyrone's goal while Bell added a penalty before Derry's Emmet McGuckin was sent-off.
Tyrone piled on the points but Mark Craig's goal put Derry in front before two Connor McAliskey frees won it.
Derry were unable to halt the determined holders, who had a star performer in midfielder Richie Donnelly.
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Heron was the first to find the net and points from Mark Craig, Bell and Mark Lynch eased the hosts further ahead, with the Red Hands losing centre back Justin McMahon to a black card.
Bell smashed home a penalty in the 23rd minute, but Tyrone hit back with a Quinn goal on the half-hour.
McAliskey and Johnny Munroe tagged on points, and at the break Derry led by two points.
Sean Cavanagh came off the bench to score a point before a Mark Bradley free gave Tyrone the lead.
Derry were awarded a second penalty in the 50th minute, which Bell again converted.
However, the loss of McGuckin to a second yellow card was an increasing problem for Damian Barton's side, and Tyrone struck a series of scores through Peter Harte, Richie Donnelly and David Mulgrew.
Derry's fourth goal came from Craig five minutes from the end, but the visitors responded with a couple of McAliskey frees to win by the narrowest of margins.
Bank of Ireland Dr McKenna Cup results
Saturday 9 January
Section C
Cavan 3-14 0-9 Ulster University
Sunday 10 January
Section A
Derry 4-6 1-16 Tyrone
Section B
Donegal 0-8 2-6 St Mary's College
Down 0-8 0-14 Fermanagh
Section C
Monaghan 2-9 0-16 Armagh
Tyrone fought back to clinch a 1-16 to 4-6 victory over Derry in a dramatic Dr McKenna Cup encounter at Owenbeg.