In 1853, Franklin Pierce appointed Gregg the Commissioner to the Kingdom of Hawaii to negotiate its annexation at the request of its king, Kamehameha III.

Gregg then accepted an appointment by President James K. Polk as United States Attorney for the District of Illinois.

In 1850, he was named the Illinois Secretary of State as a Democrat, filling the unexpired term of the deceased Horace S. Cooley.

He was a leading candidate in 1852 for the Democratic nomination as Governor of Illinois, but was defeated by Joel Aldrich Matteson.

President Andrew Johnson commissioned him receiver of public moneys for the district of lands subject to sale in the city.