Fish, currently ranked 15th, will formally overtake his friend and world number eight Roddick when the ATP world rankings are updated next week.
Roddick, struggling with a bronchial infection, made a shock early exit in the defence of his Miami title in his first game, losing to Uruguayan Pablo Cuevas on Saturday.
"I don't think I will ever feel I am the top-ranked American, Andy has had a pretty good career and he has always been top dog in my generation," Fish said of his former high school team-mate.
"I've never been in this position before. Obviously it's very humbling. This is a pretty big country and has a lot of people playing tennis. So I'll try to put it into perspective, and I will."
Fish said his goal has nothing to do with bettering Roddick and is purely personal.
"Top ten is something that I am aiming for and I will be working my butt off to get there," he said.
Fish had a surprisingly easy passage to the last four, with the normally solid Ferrer fading fast in the second set in the Florida heat.
The Spaniard lost the first set after double faulting on break point to allow Fish to go ahead 6-5.
After the game, Ferrer said he had not felt well.
"I had stomach problems all the match.
"I went to the court, and I when I ran to rallies I had a lot of pain in my stomach.
In the second set, I couldn't run anymore," he said.