On 19 March 2011, in conjunction with other U.S. Navy and Royal Navy warships, Florida fired scores of Tomahawk missiles at Libyan air defense targets as part of Operation Odyssey Dawn. The Tomahawk missile strikes allowed British, French, and allied warplanes to begin enforcing a nofly zone over Libya, preventing Muammar Gaddafi from using his air force to attack rebels in his country. This was the first combat action for the Florida or any other Ohioclass submarine. During Operation Odyssey Dawn, Florida launched 93 Tomahawk missiles, with 90 effective, out of her total magazine of about 160 missiles.

Of the four Ohioclass SSGNs in the U.S. Navy, Florida was the only one that was available for use in Operation Odyssey Dawn since she was the only one that had been assigned to cruise the Mediterranean Sea. Some other Tomahawk missiles were fired by American surface ships and by a few Royal Navy nuclear submarines.

On February 15, 2013, the crew of the USS Florida were awarded the Navy Unit Commendation having "distinguished itself in action against the enemy" during Operation Odyssey Dawn in 2011.