Frederick has argued more than fifty cases in the Supreme Court of the United States, across a wide range of issues and industries.

[6] In the case, Diana Levine sued Wyeth for failing to warn patients that the drug Phenergan could cause gangrene when administered using direct IV injection.

[12] In 2013, Frederick successfully represented Kaiser in defending a $142 million jury verdict against Pfizer for fraudulent off-label marketing of Neurontin.

[15] Frederick represented the retired players at oral argument in the district court against the NFL’s motion to dismiss the complaints on the ground of preemption under the Labor-Management Relations Act.

[20] Frederick also represented MASN through three successful Federal Communications Commission (FCC) arbitration rulings against Time Warner Cable.

[23] With Korein Tillery as co-counsel, Frederick led the outside litigation team on behalf of the National Credit Union Administration to recover more than $5.2 billion against Wall Street banks for their role in the 2007-2009 financial crisis.

Frederick's team successfully recovered from the largest banks on Wall Street for their role in causing the failures of those credit unions and earned $506.3 million in contingency fees.

In a 5–4 decision, the court held that state-law claims sounding in fraud against tobacco companies are not preempted by the express preemption provision of the federal labeling statute.

[31] The case decided in favor of petitioner Mark Janus, ruling the collection of agency fees by public sector unions unconstitutional in a 5–4 decision.

Frederick was part of the Obama-Biden Legal Policy Team and was rumored to be on President Obama's short list for Solicitor General.

[35] On May 27, 2013, the New York Times reported that President Obama was considering nominating Frederick to one of three vacancies on the United States Court of Appeals for the District of Columbia Circuit.

[38] In February 2022, Frederick was elected as a University College Foundation Fellow at his Oxford alma mater, donating $35 million toward new facilities in July 2022.

[39][40] In June 2022, Frederick was elected to the board of trustees at his alma mater, the University of Pittsburgh, and after a multi-million dollar donation in the following month, the honors college has been named after him.