[2] Southwick was in private practice as an attorney in Jackson, Mississippi with the firm Brunini, Grantham, Grower & Hewes from 1977 to 1989, serving as a partner from 1983 to 1989.

In 1989, Southwick entered government service as a Deputy Assistant Attorney General for the United States Department of Justice Civil Division.

There he supervised the one hundred and twenty-five lawyers of the Federal Programs Branch, which defends suits brought against the United States.

[3] He thereafter remained on the court of appeals until the end of 2006 when, with a nomination to a lifetime position in the federal judiciary pending, he did not run for re-election.

On January 9, 2007, President George W. Bush nominated Southwick to fill a seat on the United States Court of Appeals for the Fifth Circuit vacated by Judge Charles W. Pickering, who retired in 2004.

Bush had nominated him on June 9, 2006 to fill a vacancy on that court left by Judge William H. Barbour Jr., who retired on February 4, 2006.

In the first case, Richmond v. Mississippi Department of Human Services, Southwick joined the majority opinion upholding the decision of the Mississippi Employee Appeals Board to reinstate a white state employee (Richmond) who was fired for a single incident of referring to a black co-worker as a "good ole nigger" outside of the co-worker's presence.

The Appeals Board's decision to reinstate Richmond was based, in part, on a hearing officer's opinion that the slur was only "somewhat derogatory" and "was in effect calling the individual a 'teacher's pet.'".

[16] On writ of certiorari, the Mississippi Supreme Court agreed that "the unique circumstances of this case do not warrant imposition of the ultimate penalty of dismissal."

However, the court found the record was insufficient to uphold the Employee Appeals Board's decision that Richmond effectively receive no penalty whatsoever.

Southwick wrote for a unanimous three judge panel on an issue involving the valuation of private annuities for estate tax purposes.

In August 2018, Southwick found that the Texas Medical Board was entitled to qualified immunity for its unconstitutional warrantless search of a doctor's patient records, drawing an unusual concurrence dubitante from Circuit Judge Don Willett.