The win earned Mertens her tenth WTA singles title and first on grass, though she has won the Wimbledon women's doubles title in 2021, while also extending her winning head-to-head record against Ruse to 4-0.
"It's been an incredible week," said Mertens, who had to dig deep to save 11 match points and overcome two-time winner Ekaterina Alexandrova in Saturday's semi-final.
"I mean, yesterday, I had 11 match points against me. I managed to still win that match. It's tennis, anything can happen. So I'm very proud that I took that chance yesterday and today."
Mertens trailed 3-1 in the first set after being put under early pressure by the Romanian qualifier.
The Belgian recovered from her shaky start and saved two break points to secure a crucial hold in the fifth game, which turned the tide of the contest.
The set was brought back on serve at 3-3 after Ruse double-faulted twice, and Mertens quickly reeled off three more games to clinch the opener, with Ruse taking a lengthy medical timeout between the sets and having her thigh strapped.
The pair traded breaks halfway through the second set and Ruse was able to earn two set points at 5-4, but Mertens showed great resilience to hold serve and force a tiebreaker, which she powered through with little trouble.
"First of all, I would like to congratulate Elise. You beat me every time, so what can I say," said Ruse, who committed seven double faults in the match.
"I'm really sad and angry, but I will try next time... I'm very proud of myself. I didn't expect to be in the final here. It's such a nice tournament."