Halep had played solid tennis all week, but she struggled early on in the final and was broken on her first serve. The Romanian, who will now rise to the fourth spot in the world rankings with victory, fought back to take a tight opening set after Mladenovic had served for it at 5-4.
Mladenovic, seeded 17th, responded by deservedly taking a high quality match the distance by winning a second set tie-break. "I am very happy to have defended the title, it means a lot to me and gives me confidence for the next big tournaments", said Halep after the match.
The Frenchwoman tired in the decider as Halep took control to win her 15th career title.
Halep now has 15 titles under her belt, three of them Premier Mandatory trophies, of which this is her first this season.
The Romanian also becomes the first player to successfully defend her title in Madrid since Serena Williams did so, and the most successful player in the tournament's history, with two titles and the runner-up trophy she collected in 2014 when she lost to Maria Sharapova.