Madison Keys lifts Eastbourne title for second time
The American appeared to be cruising towards her third grass court title as she raced through the first set and led 4-1 in the second.
Kasatkina was battling the blustery conditions and a series of net cords that went in Keys' favour but found her stride to take five of the next six games.
However, the Russian, who will enter the world's top 10 next week, was broken when serving to take the second set.
Instead a marathon tie-break ensued as Kasatkina again battled back from 5-2 down to have four set points.
Keys' booming forehands though dug the world number 25 out of trouble and she eventually took the title on her fifth match point.
"It feels like home," said Keys of backing up her first-ever WTA title at Eastbourne in 2014.
"Being able to win the title here twice now makes me have very fond memories of Eastbourne."
Keys will now turn her attention to Wimbledon, where she faces British wildcard Sonay Kartal in the first round on Tuesday.
Kasatkina is in action at the All England Club on Monday against American Caroline Dolehide.