Rubio said the nation now stands at a crossroads and that the steps Congress takes in the near future could resonate across the next century.
"We will either bring on another American century, or we are doomed to witness America’s decline," said Rubio. "But another American century is fully within our reach."
On specific policy goals, Rubio kept in step with many of his conservative counterparts, calling on Congress to control the debt, make the tax code more predictable, and ease regulations.
On the matter of foreign affairs, however, Rubio differentiated himself from some Tea Party colleagues by describing a vision in which the U.S. continues to play a central role in the world.
"America is still the only watchman on the wall of world freedom," he said, invoking President John F. Kennedy. "What will the world look like if America declines?"
Rubio also borrowed a phrase from President Ronald Reagan by calling on America to remain the "shining city on the hill."
Rubio was the final senator from the freshman class to deliver his inaugural speech in the Senate. Despite speculation that he could be a future presidential candidate, Rubio has kept a low profile so far.
The Senate adjourned at 6:58 p.m. on Tuesday.