David de la Cruz and Dylan van Baarle moved up to fifth and sixth respectively overall at Coppi e Bartali after an unfortunate stage two for Team Sky.
However, 2018 winner Diego Rosa was less fortunate and suffered a puncture at a crucial point on the final climb and finished one minute shy of former teammate Landa, which will severely dent his GC hopes.
Lucas Hamilton (Mitchelton-Scott) was the only rider able to stay in contention with Landa once the former Team Sky rider attacked with under 15 kilometres to go and he was rewarded with the leader's jersey, holding a 26 second lead over Van Baarle and De la Cruz.
Sport Director Oli Cookson was pleased with the response of the team in such adversity, telling TeamSky.com: "Diego had a puncture at the worst possible time on the final climb which has really put paid to his GC hopes.
"De La Cruz was also unlucky and had a puncture with one lap remaining, but after a long chase he was able to get back on and finish in the chasing pack - it was certainly a challenging day!"
1, Lucas Hamilton (Mitchelton-Scott) 6:23:33
2. Damien Howson (Mitchelton-Scott) +16"
3. Nick Schultz (Mitchelton-Scott ) s.t.
4. Mikel Landa (Movistar) s.t.
5. David de la Cruz (Team Sky) +26"
6. Dylan van Baarle (Team Sky) s.t.