George was named after his mother's elder brother, King George I of Greece. As an infant, he was stronger and healthier than his brother Nicholas. He could be described as a typical Romanov. George was tall, unlike his elder brother Nicholas, handsome and full of fun. He was always getting into mischief and, because his mother had a great weakness for him, getting away with it. Like his siblings, he was brought up in a spartan fashion in the English manner. They slept on camp beds, rose at six and took a cold bath, although occasionally they were allowed to take a warm bath in their mother's bathroom. Breakfast was usually porridge and black bread; mutton cutlets or roast beef with peas and baked potatoes were served for lunch; bread, butter and jam at tea-time. Cake was a special treat. Nicholas and George had a sitting-room, dining-room, play-room and bedroom, all simply furnished. The only trace of ostentation was an icon surrounded by pearls and precious stones. George's mother taught him that family life was important. Because of his parents' happy marriage, he was brought up in an atmosphere of love and security missing in many royal households. On 27 May 1883, George's parents were crowned in a magnificent ceremony in the Uspensky Cathedral in the Kremlin in Moscow. The Emperor and Empress received the homage of the Imperial Family, including their sons, Nicholas and George, both in uniform. It was a major occasion in the life of the young Grand Duke. The family lived mostly in the security of the palace at Gatchina.
George was considered to be the cleverest of the Imperial children. He was also outgoing, like his mother. George and Nicholas shared the same tutors, but studied in adjoining rooms. They followed the course of the Academy of the Russian General Staff. Their tutors were distinguished professors. Their English teacher, Charles Heath, had once been tutor to their uncles, Grand Dukes Sergei and Pavel. Both brothers spoke and wrote faultless English. From Mr. Heath they acquired a love of sport, particularly shooting and fly-fishing. They also spoke fluent French and passable German and Danish. George displayed signs of a promising career in the Navy before falling ill with tuberculosis in 1890.
The Emperor and Empress both decided to send Nicholas and George on a nine-month-long trip to Japan in 1890. George would go as a naval cadet and Nicholas to complete his education by seeing something of the world. Their mother hoped the warm sun and the sea air would improve George's health. They left Gatchina on 4 November 1890. The Empress had never been separated from her sons for such a long time and she missed them terribly. "You cannot imagine how sad and hard it is to be without you, my angel, and how dreadfully it hurts to think of this long separation", she wrote sadly. Nicholas and George first went by warship to Athens where they were joined by their cousin, Prince George of Greece, known as "Greek Georgie". From there, they traveled to Egypt. From Bombay in India, Nicholas telegraphed that his brother George had to remain on ship because he had trouble with his leg. Although George assured his parents that he was perfectly well, they were suddenly informed he had a fever and would have to return home. The Empress was alarmed. "You can't imagine in what anguish I have passed these last few days", she wrote. "In spite of all the reasoning ... I had to take things calmly, and to tell myself that it ... is only this horrible malaria that will pass with a change of air ..."  George, in fact, had acute bronchitis and was sent back to Athens where he could be examined by the Imperial doctors. The Empress was distressed for both brothers: George, whose disappointment she felt deeply and Nicholas, who was now deprived of his brother's company.
In November 1894, Alexander III died and Nicholas mounted the throne as Emperor. At the time, Nicholas had no children, thus according to the laws of succession of the Russian Empire, the Grand Duke George became Tsarevich (formally Tsesarevich, denoting the heir presumptive or heir apparent to the throne as opposed to any son of the Tsar, although the latter title fell into disuse in 1721 and was gradually supplanted by the more specific use of Tsarevich). George's ill-health had forced him to relocate to Likani. It was impossible for him to return to St. Petersburg for the funeral of his father, Alexander III. The doctors had forbidden it. Nicholas wrote to his brother, "... constantly pray to God to send you a full and speedy recovery, and to comfort you, because it is so much more difficult to be alone after such great sorrow than it is for us who are at least together!"  George also missed the christenings of Nicholas' elder daughters, Olga and Tatiana. Shortly after the birth of Nicholas' third daughter, Maria, in June 1899, George wrote to his brother, "I am terribly sad that I have not yet been able to see your daughters and get to know them; but what can I do! It means it's not my fate, and everything is the will of God." 
Visits from his mother to Likani were greatly enjoyable. In 1895, George and his mother visited Denmark. They had not seen their Danish relatives for four years. It was sad as it was the first time for both of them without the late Tsar. Then suddenly, his health deteriorated, "Yesterday, in the garden, he expectorated some blood...that frightened me more than I can tell - the surprise of it was shocking, because he had been so well of late...I am quite desperate that this should have happened here"  As a result, George was forbidden to smoke and confined to bed until he was fit enough to return to Likani. Writing to Nicholas back home once again, George said about his trip to Denmark, "Of course it was good to see the family after 4 years, but it did not really do me any good, as I lost more than 5 pounds which I had put on with such difficulty in May and June. I also get out of breath more easily. So these are the results of my trip. Very annoying." 
George died suddenly in Abastumani, on 9 August 1899, at the age of 28. He had been out alone on his motorcycle and some hours later, when he failed to return, his worried staff sent out a search party. By the time they found him it was too late. A peasant woman had discovered him collapsed at the side of the road, blood oozing from his mouth as he struggled to breathe. She supported him in her arms until he died.
The news reached Nicholas by telegram and he had the difficult task of telling his mother. She broke down and wept. He had seldom been out of her thoughts for the last few years and his death came as a terrible shock. His family were completely devastated. Nicholas was especially grief-stricken at losing his younger brother and childhood playmate. Grand Duke Konstantin Konstantinovich wrote, "Everyone was struck, as if by lightning, by this sad and unexpected news. Queen Victoria wrote to Nicholas II, "Pray accept the expression of my sincerest sympathy in this great sorrow, for I know the affection you had for your poor brother Georgy, whose life was so sad and lonely." The Dowager Empress telegraphed Queen Victoria, "Thank you so much for kind sympathy in this terrible sudden bereavement... My poor dearest son died quite alone. Am heartbroken."