Little is known of George Lowther's life until he became first mate on the English slave ship Gambia Castle in 1721. The vessel was docked for months off the coast of Gambia, Africa, waiting for a cargo of slaves, a delay that didn't help the crew, who were suffering from dysentery, malaria, and scurvy. Lowther and his crewmates grew weary of waiting and dealing with illness, so they decided to sail away with the Gambia Castle while the captain was ashore. Once that was accomplished, the crew elected Lowther as their new captain and decided to go on the account.

While sailing for the Grand Cayman Islands, Lowther and his crew came across the English naval ship HMS Greyhound, which was captained by Benjamin Edwards. Lowther surprised the Greyhound at anchor, beat the crew, then set the ship afire and sailed away. Following that incident, Lowther sailed with pirates Charles Harris and Edward Low, and took a few prizes with them, but they parted company after a short time. In 1722, Lowther and his men put up at a small cay known as Blanquilla, north of Venezuela, to repair his ship. The crew had almost completed the job when a Royal sloop, the HMS Eagle captained by Walter Moore, spotted them and attacked. The pirates attempted to run, but only about a dozen — including Lowther — escaped through a cabin window of the ship and hid on the island. Moore's men set off to find the escapees with plans to bring them to justice. They captured most of them, but when they found Lowther he was dead, with a pistol in his hand and a bullet in his head. Lowther, it seemed, preferred taking his own life to facing a trial and the hangman's noose.