World number 12 Norrie won the tournament in Los Cabos, Mexico last year but faced a tall task defending his crown against the top-ranked Medvedev.
Little separated the two in a tense first set as both players converted their early opportunities.
British number one Norrie successfully repelled a set point at 5-4 but was unable to prevent Medvedev converting on his second attempt.
The Russian was in cruise control from there, racing home in the second to capture his 14th tour-level trophy with a 7-5 6-0 win.
It marks Medvedev’s first tour victory since last year’s US Open.
“I fought as hard as I could do, but Daniil was too good,” said Norrie, 26. “Well done to you and your team. You definitely deserve it this week.
“I just want to say a big thank you to everyone for supporting me. I love playing in Mexico and that is the reason why I come back. I really feel good here.”