Landa attacked on the 14 per cent ramp at the finish to distance himself from the peloton, with second place Sergey Firsanov (Gazprom-Rusvelo) finishing four seconds later.
Damiano Cunego, winner of the Giro d'Italia in 2004, claimed third on the stage, 13 seconds down on Landa.
Landa's time gap over the leading Astana rider, Jakob Fuglsang, gives him the overall lead by 10 seconds over the Dane with two more mountainous stages to finish the race.
Giro del Trentino stage two, Arco - Anras (220km)
1. Mikel Landa (Esp) Team Sky, 5-18-12
2. Sergey Firsanov (Rus) Gazprom-Rusvelo, at 4s
3. Damiano Cunego (Ita) Nippo-Vini Fantini, at 13s
4. Giulio Ciccone (Ita) Bardiani CSF, at 14s
5. Jakob Fuglsang (Den) Astana, st
General classification after stage two
1. Mikel Landa (Esp) Team Sky, 5-31-46
2. Jakob Fuglsang (Den) Astana, at 10s
3. Sergey Firsanov (Rus) Gazprom-Rusvelo, at 15s
4. Michele Scarponi (Ita) Astana, at 22s
5. Romain Bardet (Fra) Ag2r La Mondiale, at 24s
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