Murray rallied from a game down in the final set and went on to beat the third-seeded Spaniard 2-6, 6-4, 7-6 (7-1) in a grueling 2-hour, 45-minute match at Crandon Park in Key Biscayne.
The Briton broke ahead 5-4 in third, but Ferrer won the next two games and set up championship point after Murray mishit a volley.
In the final game, Ferrer challenged a Murray shot as too long but was overruled upon video review, triggering a slide that ended in a lopsided tiebreak loss.
Murray's 26th career title and second in Miami will likely enable him to bypass Roger Federer for the world No. 2 ranking. He improved to 6-1 lifetime against Ferrer on hard courts.
Ferrer fell to 0-13 in finals against Top 5 players.
Despite the loss, Ferrer is expected to move up to the world No. 4 spot.