Of the 36 inmates who staged 14 escape attempts over the 29 years that Alcatraz served as a federal penitentiary, twenty-three were recaptured, six were shot and killed, two drowned, and five (three being Morris and the Anglins and the other two being Theodore Cole and Ralph Roe) are listed as "missing and presumed drowned".

Since the ostensible escape of the three men, there have been many a sighting of them reported as well as lead to their whereabouts submitted; some of which have been discounted, others, taken seriously. A day after the escape, a man claiming to be John Anglin had called a lawyer, Eugenia MacGowan, in San Francisco to arrange a meeting with the U.S. Marshals office. When MacGowan refused, the caller terminated the phone call. The FBI dismissed the call as a prank. In January 1965, the FBI investigated a rumor that Clarence Anglin was living in Brazil. It was considered so significant that agents were dispatched to South America to find him. A male tipster called the Bureau in 1967 claiming to have been at school with Morris and having known him for 30 years. He said he had bumped into him in Maryland and described him as having a small beard and mustache', but refused to give further details.

It helped to ensure their mutual trust that they already knew each other from their time in an Atlanta prison years before. Over the subsequent six months, the men widened the ventilation ducts beneath their sinks using discarded saw blades found on the prison grounds, metal spoons smuggled from the mess hall, and an electric drill improvised from the motor of a vacuum cleaner. The men concealed the progress of their holes with walls of painted cardboard, and the noise of their work with the louder noise of Morris’ accordion on top of the ambient din of music hour.

The four inmates were no sooner assigned adjacent cells in December 1961 than they began formulating the escape plan together, though always under the leadership of Morris, the chief mastermind and unilateral orchestrator of the plot.

The men concealed their absence while working outside their cells and after the escape itself by sculpting dummy heads from a home-made paper-mâché-like mixture of soap, toothpaste, concrete dust, and toilet paper, and giving them a realistic appearance with paint from the maintenance shop and hair from the barbershop floor. With towels and clothing piled under the blankets in their bunks and the dummy heads positioned on the pillows, they appeared to be sleeping.

Once the holes were wide enough to pass through, the escapees nightly accessed the utility corridor left unguarded directly behind their cells' tier and climbed to the vacant top level of the cellblock, where they set up a clandestine workshop unbeknownst to prison staff. Here, with over fifty raincoats among other stolen and donated materials, they constructed life preservers, based on a design one of them chanced to find in Popular Mechanics, as well as a six-by-fourteen-foot rubber raft, the seams carefully stitched by hand and sealed by steam pipes' heat. Having manufactured the raft, they inflated it with a concertina ingeniously rigged to serve as bellows and furnished the necessary paddles from scrap wood and pilfered screws. Finally, they climbed up a ventilation shaft bound for the roof, and, finding a ponderous fan-grille in the way, removed the rivets holding it in place.

On the night of June 11, 1962, with all preparations in place, the men began their escape. However, the cement employed to shore up crumbling concrete around West's vent had hardened, diminishing the hole in size and fixing the grill in place. By the time he managed to remove the grill and re-widen the hole to egress, the others had already left, as he was soon to discover; he busted out to the prison roof only to return to his cell around sunrise and go to sleep. West went on to cooperate fully with investigators and give them a detailed description of the escape plan, in consequence of which he was not punished for his role in it.

Frank Lee Morris (September 1, 1926 – disappeared June 11, 1962) was born in Washington, D.C.[19] He was abandoned by his mother and father during his childhood, and orphaned at age 11, The Anglin brothers, John William (May 2, 1930 – disappeared June 11, 1962) and Clarence (May 11, 1931 – disappeared June 11, 1962) were born into a family of thirteen children in Donalsonville, Georgia. Their parents, George Robert Anglin and Rachael Van Miller Anglin, were seasonal farmworkers; in the early 1940s, Allen Clayton West (March 25, 1929 – December 21, 1978) was born in New York City. He was imprisoned for car theft in 1955, first at Atlanta Penitentiary, then at Florida State Prison. After an unsuccessful escape attempt from the Florida facility, he was transferred to Alcatraz in 1957 and became inmate AZ1335.

From the service corridor, Morris and the Anglins climbed the ventilation shaft to the roof. Guards heard a loud crash as they broke out of the shaft, but since nothing further was heard, the source of the noise was not investigated. Hauling their gear with them, they descended 50 feet (15 m) to the ground by sliding down a kitchen vent pipe, then climbed two 12-foot (3.7 m) barbed-wire perimeter fences. At the northeast shoreline, near the power plant—a blind spot in the prison's network of searchlights and gun towers they inflated their raft with the concertina. At some time after 10 p.m., investigators estimated, they boarded the raft, launched it and departed toward their objective, Angel Island, two miles to the north.

The escape was not discovered until the morning of June 12, 1962, due to the successful dummy head ruse. At the time of the escape, Warden Olin G. Blackwell was on vacation in Lake Berryessa in Napa County, California, and he did not believe the men could have survived the waters and make it to shore. In a joint effort, multiple military and law-enforcement agencies conducted extensive air, sea, and land search over the next 10 days. On June 14, a Coast Guard cutter picked up a paddle floating about 200 yards (180 m) off the southern shore of Angel Island.

On the same day and in the same general location, workers on another boat found a wallet wrapped in plastic complete with names, and addresses, and photos of the Anglins' friends and relatives. On June 21, shreds of raincoat material, believed to be remnants of the raft, were found on a beach not far from the Golden Gate Bridge. The following day, a prison boat picked up a deflated life jacket made from the same material 50 yards (46 m) off of Alcatraz Island. No other physical evidence of the men's fate was ever found. According to the final FBI report, the escapee's raft was never recovered.

On December 16, 1962, inmate John Paul Scott successfully swam a distance of 2.7 nautical miles (5.0 km; 3.1 mi) from Alcatraz to Fort Point, at the southern end of the Golden Gate Bridge. He was found there by teenagers, suffering from hypothermia and exhaustion. After recovering in Letterman General Hospital, he was immediately returned to Alcatraz. It is the only proven case of an Alcatraz inmate reaching the shore by swimming. Scott's escape, undertaken in slightly more unfavorable conditions than Morris and the Anglins faced, and using a means of flotation that was far inferior to the raft constructed by Morris and the Anglins ( Scott made water wings by inflating stolen rubber gloves ) shook the line of reasoning that Morris and the Anglins had likely drowned. Today, a multitude of athletes swim the same Alcatraz to Fort Point route as part of one of two annual triathlon events.

Because the penitentiary cost much more to operate than other prisons (nearly $10 per prisoner per day, as opposed to $3 per prisoner per day at Atlanta), and half a century of saltwater saturation had severely eroded the buildings, then-Attorney General Robert F. Kennedy ordered the penitentiary closed on March 21, 1963.

Escape from Alcatraz is a 1979 American prison thriller film directed by Don Siegel. It is an adaptation of the 1963 non-fiction book of the same name by J. Campbell Bruce and dramatizes the 1962 prisoner escape from the maximum-security prison on Alcatraz Island. The film stars Clint Eastwood and features Patrick McGoohan, Fred Ward, Jack Thibeau, and Larry Hankin. Danny Glover appears in his film debut. Escape from Alcatraz marks the fifth and final collaboration between Siegel and Eastwood, following Coogan's Bluff (1968), Two Mules for Sister Sara (1970), The Beguiled (1971) and Dirty Harry (1971).

The FBI closed its file on December 31, 1979, after a 17-year investigation. Their official finding was that the prisoners most likely drowned in the cold waters of the bay while attempting to reach Angel Island, it being unlikely that they made it the 1.25 miles to shore with the strong ocean currents and the cold seawater temperatures ranging between 50 and 55 degrees Fahrenheit. They cited the remnants found of the raft as well as the personal effects of the men, as evidence to bolster the official line that the raft broke up and sank at some point after having launched from Alcatraz and that the three convicts tried to swim for it, but then surely succumbed to hypothermia, their bodies swept to sea by the rapid currents of the San Francisco Bay. However, the FBI did hand the investigation over to the U.S. Marshals Service, who have not closed theirs since. As Deputy U.S. Marshal Michael Dyke told NPR in 2009: "There's an active warrant, and the Marshals Service doesn't give up looking for people." Dyke also pointed out that the bodies of two out of every three people who go missing in San Fransisco Bay are eventually recovered.

In 1989, a woman who only identified herself as "Cathy" called Unsolved Mysteries tip line to report that she recognized a photo of Clarence Anglin, as a man who lived on a farm near Marianna, Florida. The brothers also were linked to the area by a woman, who recognized a photo of Clarence Anglin and said he lived near Marianna. She correctly identified his eye color, height, and other physical features. Another witness identified a sketch of Frank Morris, saying it bore a striking resemblance to a man she had seen in the area.