A win would have seen Halep overtake world number one Naomi Osaka but she lost 6-4 6-4.
The title is the biggest of Bertens’ career and she will climb to fourth in the rankings on Monday, making her the highest-ranked Dutchwoman in history.
She also becomes the first woman to win in Madrid without dropping a set.
Halep is the fourth Grand Slam champion Bertens has beaten during the tournament and she will now been seen as one of the favourites for the French Open, which begins on 27 May.
Both players struggled to hold serve with eight breaks across the two sets – three to Halep and five to Bertens – but the Dutchwoman was the more dominant.
Last year’s runner-up hit 25 winners and four aces with her forehand in particular causing problems.