Keys, seeded second, ignored sweltering temperatures on the south coast to see off the world number 112 in 93 minutes.
It was the 31-year-old's first title since she clinched her maiden Grand Slam crown at the Australian Open last year.
Keys joins an illustrious group of three-time champions on the Eastbourne grass, alongside Chris Evert and Martina Navratilova.
In her first final since finishing as the Trophee Clarins runner-up in Paris in May, the world number 27 avenged a semi-final defeat against Maria on grass at Queen's Club last year.
Keys' first WTA title came at Eastbourne 12 years ago and she won a second in 2023.
She maintained her dominance at the event, securing an 11th title on the women's tour in her 16th career final.
She was in charge throughout against the 38-year-old Maria and faced just one break point.
Having also won the Birmingham event 10 years ago, Keys now owns four career grass-court titles.
It was the perfect preparation for Wimbledon, which starts on Monday, with Keys never managing to go beyond the quarter-finals at the All England Club.
She will face compatriot Kayla Day in the first round on Tuesday.
The men's final at Eastbourne between French sixth seed Ugo Humbert and Belgium's Zizou Bergs was halted by heavy rain after just three games of the first set.
World number 30 Humbert will take a 2-1 lead into the resumption on Sunday, with the pair scheduled to meet again in the Wimbledon first round next week.
It is only the third time since 1990 that two finalists from a tournament have faced each other in the first round of a Grand Slam the following week.