The SKODA driver concluded a fruitful morning with a 1.1-second winning margin in the 14.31km Tejeda stage over team-mate Jan Kopecky.
Luis Monzon of Peugeot was third on the stage, and third overall - 31.1 seconds adrift of Mikkelsen.
“I was a little bit careful on the downhill section but other than that it was a clean stage, I was saving the brakes,” said Mikkelsen.
Kopecky said: “For us it was okay but it seems Andreas was motivated and pushing hard. The car is working well but this is our first proper tarmac rally together [with co-driver Pavel Dresler] so we are taking our time.”
Hermann Gassner Jr was fourth fastest, while in the battle for fifth position Alberto Hevia moved back ahead of Sepp Wiegand by 2.8s in a fascinating back-and-forth tussle.
1 Mikkelsen (Škoda Fabia S2000) 28:23.2
2 Kopecký (Škoda Fabia S2000) 28:26.8
3 Monzón (Peugeot 207 S2000) 28:54.3
4 Gassner (Škoda Fabia S2000) 29:00.8
5 Hevia (Škoda Fabia S2000) 29:09.3
6 Wiegand (Škoda Fabia S2000) 29:10.5
7 Pérez (Peugeot 207 S2000) 29:39.4
8 Vinyes (Suzuki Swift S1600) 30:03.8
9 Tamrazov (Ford Fiesta S2000) 30:04.7
10 Antxustegi (Suzuki Swift S1600) 30:20.7