As a federal judge, Whittemore presided over a number of high-profile cases, including a lawsuit against Major League Baseball to challenge its draft procedure, and the Terri Schiavo case, after the United States Congress had specifically given the Middle District of Florida jurisdiction to hear the seven-year-long fight over whether the brain-damaged Schiavo should be taken off life support.

In 1985, Whittemore successfully argued before the United States Supreme Court in Wainwright v. Greenfield, 474 U.S. 284 (1986), that a criminal suspect's silence after he received the Miranda warning could not be used at trial to discredit his insanity defense.

Viera, represented by attorney Alan Gura and agent Joe Kehoskie, had claimed that the MLB draft was discriminatory because it had a different residency requirement for Cubans, but Whittemore decided that whatever financial loss Viera suffered from being subject to the draft did not satisfy the federal injunction requirement of irreparable harm.

Whittemore presided over the criminal trial of Gerald and Betty Payne, the founders of Greater Ministries International Church.

Betty was sentenced to over 12 years, which was increased from what Whittemore initially considered after she repeated a claim they were the innocent victims of government persecution and their religious freedoms were being violated.

The Schindlers disputed that their daughter was in a persistent vegetative state or that she would have wanted to have life support withdrawn, but Schiavo, his expert witnesses, and court-appointed physicians had successfully argued the contrary before Florida trial court judge, George Greer.

As appropriate for the federal standard of review for a TRO motion, his ruling avoided the issue of whether the Congressional grant of jurisdiction was unconstitutional, as Michael Schiavo and most legal scholars had argued.

Though three of the four elements of the federal TRO standard, including irreparable harm, were clearly satisfied by Schiavo's imminent death, Whittemore did not believe the Schindlers ultimately had a substantial likelihood of prevailing, but instead found each of their claims "without merit."

The Eleventh Circuit affirmed Whittemore's "carefully thought-out decision" in a 2-1 ruling on March 23,[2] and denied rehearing en banc later the same day, 10–2.

During the hearing, the protesters that still surrounded the area outside the courthouse were temporarily evacuated, so that law enforcement could detonate a suspicious bag that turned out to be harmless.

Whittemore closed his order by conveying the court's "appreciation for the difficulties and heartbreak the parties have endured through this lengthy process."