Appleby's crew included:Jack Mullaney (1929–1982) as 24-year-old Lieutenant Rex St. John, wealthy, handsome, and ambitious but vain
Jay C. Flippen (1899–1971) as the cantankerous Chief Petty Officer Homer Nelson
Jack Albertson (1907–1981), as Lieutenant Commander Virgil Stoner, the ship's executive officer who delivered orders from the ship's unseen captain, heard only over speakers
Harvey Lembeck (1923–1982), earlier on Phil Silvers' Sergeant Bilko series, portrayed Seaman Gabby Di Julio
Beau Bridges (born 1941), son of Lloyd Bridges, as Seaman Howard Spicer
Robert Sorrells (born 1930) as Seaman Claude White
John McGiver (1913–1975), a popular character actor who later starred on CBS's Many Happy Returns, appeared as Stone's brother-in-law, the psychologist Arthur Ainsley, who argued that the ship's crew was unhappy and hiding deep-seated depression.
Ken Berry (1933-) as Lt. Melton / Calucci
Ensign O'Toole was based on All the Ships at Sea and Ensign O'Toole and Me, two books by William Lederer, who served as a consultant on the series. Though there was no second season of production, Ensign O'Toole was repeated on NBC through September 15, 1963, and ABC aired reruns of the show from March to September 1964.
The real-life U.S. Navy destroyer USS Frank E. Evans (DD-754), which was launched on October 3, 1944 and commissioned on February 3, 1945, portrayed Appleby. On June 3, 1969, Frank E. Evans was cut in half in a collision with the Royal Australian Navy aircraft carrier HMAS Melbourne with the loss of 74 of her crew. Her bow sank almost immediately, and her stern was sunk as a target in Subic Bay in the Philippines.
Ensign O'Toole was aired opposite CBS's long-running Lassie at the 7 p.m. Eastern time slot on Sundays. ABC that season aired repeats of Robert Young's Father Knows Best in the same time slot.
After Ensign O'Toole, Dean Jones starred in numerous Disney films from 1965 to 1977.
During her tour of duty, Appleby anchored in numerous ports: Hong Kong, South Korea, the Arctic, the South Pacific, and its home port, San Diego, California. The opening episode entitled "Operation Kowana" introduces the cast. The sailors are given shore leave with a stern warning to mind their behavior when they land in the Japanese port of Kowana.
The second episode, "Operation Model T", which aired on September 30, 1962, Terence O'Toole buys a Model T on a French island in the South Pacific and camouflages it in pieces aboard the ship. After reaching California, O'Toole has the car reassembled, and an admiral, who is an antique car collector, sees it on the dock and thus foils the ensign's plans.
In the third episode, October 7, 1962, entitled "Operation Daddy", O'Toole has to assemble emergency leave papers for Seaman White, whose wife in Omaha, Nebraska, is about to give birth.
In "Operation Benefit" (October 14, 1962), while Appleby was in South Korea, Ensign O'Toole and the crew put on the "Foster Father's Follies" show to raise money to adopt Korean orphans. The Kim Sisters provided the entertainment. Dick Powell (1904–1963), owner of Four Star Television, which produced the series, guest starred in the episode. At the time of his appearance, Powell had fewer than three months to live.
Soupy Sales guest starred in "Operation Jinx" on October 21, 1962, as Seaman Jerome J. Johnson. Chief Nelson warns of trouble because Johnson is believed to be a bad-luck omen.
In "Operation Holdout" on October 28, 1962, the crew found four stranded soldiers, two American and two Japanese, who think World War II is still underway.
Harry Morgan (1915–2011), later Colonel Sherman T. Potter on CBS's M*A*S*H*, appeared in "Operation Mess" on November 18, 1962. O'Toole is puzzled why the crew is grumbling about the food when Charlie was previously known as a superior chef. Ken Berry's character refers to O'Toole's first name as Terence.
In "Operation Potomac" on December 9, 1962, with guest star Richard Eastham, O'Toole tries to determine why someone sent him a dress while the ship is in port near Washington, D.C. The unsolicited gift inspired lots of ribbing from his fellow crew members. Eventually, O'Toole learns the dress was for a female naval officer with the same name assigned to the same installation.
"Operation Gaslight" on December 16, 1962, featured Steve Franken, Chatsworth Osborne, Jr., in CBS's The Many Loves of Dobie Gillis, as Ensign Bender, a by-the-book sailor from the United States Naval Academy at Annapolis, Maryland. O'Toole decides to "initiate" Bender by convincing him that he has contracted an unusual nautical disease.
In "Operation Swindle" on December 30, 1962, Rosemary De Camp, who played the sister of Bob Cummings in an earlier NBC comedy series, guest starred as a Southern belle who strips Chief Nelson of his bank book.
"Operation Intrigue" on January 13, 1963, is set in Hong Kong, then a British colony. O'Toole volunteered to help Scotland Yard find a jewel thief by going undercover.
"Operation Royalty" on January 27, 1963, offers Dennis Cross in the role of the "Captain of the Guard".
In "Operation: Arrivederci" on March 5, 1963, O'Toole tries to help a struggling artist, an attractive young woman. He once again mentions his name is Terence.
In "Operation Stowaway" on March 24, 1963, Nita Talbot appears as Grapunia, a young girl who stows away on the Appleby, and the crew goes overboard to win her favor.
In "Operation: Physical", a conversation between O'Toole and St. John reveals that the two officers are twenty-four years of age. O'Toole remarks that St. John wouldn't like to be in the position of Lieutenant Commander Virgil Stoner, commanding junior officers half his age. St. John jokes that he wouldn't like that either, "who wants to be on the ship with a bunch of twelve-year old officers?" The episode later features a short cameo by Gary Crosby, playing a friend of O'Toole's masquerading as a doctor.
In "Operation Tubby" on April 14, 1963, Stubby Kaye (1918–1997) guest starred as Tubby Mason, a compulsive eater on the verge of being discharged from the Navy for obesity. He is ordered to go on a crash diet.
The final episode, "Operation Geisha", has Jack Carter as a con man who must return money to an irate victim. He and a partner open a reverse geisha house.