Inspired by her teacher, physicist Ludwig Boltzmann, Meitner studied physics and became the second woman to obtain a doctoral degree in physics at the University of Vienna in 1905 ("Wärmeleitung im inhomogenen Körper"). Women were not allowed to attend institutions of higher education in those days, but thanks to support from her parents, she was able to obtain private higher education, which she completed in 1901 with an "externe Matura" examination at the Akademisches Gymnasium. Following the doctoral degree, she rejected an offer to work in a gas lamp factory. Encouraged by her father and backed by his financial support, she went to Berlin. Max Planck allowed her to attend his lectures, an unusual gesture by Planck, who until then had rejected any women wanting to attend his lectures. After one year, Meitner became Planck's assistant. During the first years she worked together with chemist Otto Hahn and discovered with him several new isotopes. In 1909 she presented two papers on beta radiation.

In 1912 the research group Hahn - Meitner moved to the newly founded Kaiser-Wilhelm-Institut (KWI) in Berlin - Dahlem, south west in Berlin. She worked without salary as a "guest" in Hahn's department of Radiochemistry. It was not until 1913, at 35 years old and following an offer to go to Prague as associate professor, that she got a permanent position at KWI.

In the first part of the First World War (World War I), she served as a nurse handling X-ray equipment. She returned to Berlin and her research in 1916, but not without inner struggle. She felt in a way ashamed of wanting to continue her research efforts when thinking about the pain and suffering of the victims of war and their medical and emotional needs.

In 1917, she and Hahn discovered the first long-lived isotope of the element protactinium. That year, Meitner was given her own physics section at the Kaiser Wilhelm Institute for Chemistry. In 1923, she discovered the cause, known as the Auger effect, of the emission from surfaces of electrons with 'signature' energies. The effect is named for Pierre Victor Auger, a French scientist who independently discovered the effect in 1925.

In 1930, Meitner taught a seminar on nuclear physics and chemistry with Leó Szilárd. With the discovery of the neutron in the early 1930s, speculation arose in the scientific community that it might be possible to create elements heavier than uranium (atomic number 92) in the laboratory. A scientific race began between Ernest Rutherford in Britain, Irène Joliot-Curie in France, Enrico Fermi in Italy, and the Meitner - Hahn team in Berlin. At the time, all concerned believed that this was abstract research for the probable honour of a Nobel prize. None suspected that this research would culminate in nuclear weapons.

When Adolf Hitler came to power in 1933, Meitner was acting director of the Institute for Chemistry. Although she was protected by her Austrian citizenship, all other Jewish scientists, including her nephew Otto Frisch, Fritz Haber, Leó Szilárd and many other eminent figures, were dismissed or forced to resign from their posts. Most of them emigrated from Germany. Her response was to say nothing and bury herself in her work (she later acknowledged, in 1946, that "It was not only stupid but also very wrong that I did not leave at once.").

After the Anschluss, her situation became desperate. In July 1938, Meitner, with help from the Dutch physicists Dirk Coster and Adriaan Fokker, escaped to the Netherlands. She was forced to travel under cover to the Dutch border, where Coster persuaded German immigration officers that she had permission to travel to the Netherlands. She reached safety, though without her possessions. Meitner later said that she left Germany forever with 10 marks in her purse. Before she left, Otto Hahn had given her a diamond ring he had inherited from his mother: this was to be used to bribe the frontier guards if required. It was not required, and Meitner's nephew's wife later wore it.

Meitner was lucky to escape, as Kurt Hess, a chemist who was an avid Nazi, had informed the authorities that she was about to flee. However, unknown friends only checked after they knew she was safe. An appointment at Groningen University did not come through, and she went instead to Stockholm, where she took up a post at Manne Siegbahn's laboratory, despite the difficulty caused by Siegbahn's prejudice against women in science. Here she established a working relationship with Niels Bohr, who travelled regularly between Copenhagen and Stockholm. She continued to correspond with Hahn and other German scientists.

Hahn and Meitner met clandestinely in Copenhagen in November to plan a new round of experiments, and they subsequently exchanged a series of letters. Hahn then performed the difficult experiments which isolated the evidence for nuclear fission at his laboratory in Berlin. The surviving correspondence shows that Hahn recognized that fission was the only explanation for the barium, but, baffled by this remarkable conclusion, he wrote to Meitner. The possibility that uranium nuclei might break up under neutron bombardment had been suggested years before, notably by Ida Noddack in 1934. However, by employing the existing "liquid-drop" model of the nucleus, Meitner and Frisch were the first to articulate a theory of how the nucleus of an atom could be split into smaller parts: uranium nuclei had split to form barium and krypton, accompanied by the ejection of several neutrons and a large amount of energy (the latter two products accounting for the loss in mass). She and Frisch had discovered the reason that no stable elements beyond uranium (in atomic number) existed naturally; the electrical repulsion of so many protons overcame the "strong" nuclear force. Meitner also first realised that Einstein's famous equation, E = mc², explained the source of the tremendous releases of energy in atomic decay, by the conversion of the mass into energy.

A letter from Bohr, commenting on the fact that the amount of energy released when he bombarded uranium atoms was far larger than had been predicted by calculations based on a non-fissile core, had sparked the above inspiration in December 1938. Hahn claimed that his chemistry had been solely responsible for the discovery, although he had been unable to explain the results.

It was politically impossible for the exiled Meitner to publish jointly with Hahn in 1939. Hahn and Fritz Strassmann had sent the manuscript of their paper to Naturwissenschaften in December 1938, reporting they had detected the element barium after bombarding uranium with neutrons; simultaneously, they had communicated their results to Meitner in a letter. Meitner, and her nephew Otto Robert Frisch, correctly interpreted their results as being nuclear fission. Frisch confirmed this experimentally on 13 January 1939.

Meitner recognized the possibility for a chain reaction of enormous explosive potential. This report had an electrifying effect on the scientific community. Because this could be used as a weapon, and since the knowledge was in German hands, Leó Szilárd, Edward Teller, and Eugene Wigner together jumped into action, persuading Albert Einstein, who had the celebrity, to write President Franklin D. Roosevelt a warning letter; this led eventually to the establishment several years later of the Manhattan Project. Meitner refused an offer to work on the project at Los Alamos, declaring "I will have nothing to do with a bomb!" Meitner said that Hiroshima had come as a surprise to her, and that she was "sorry that the bomb had to be invented."

In Sweden, Meitner was first active at Siegbahn's Nobel Institute for Physics, and at the Swedish Defence Research Establishment (FOA) and the Royal Institute of Technology in Stockholm, where she had a laboratory and participated in research on R1, Sweden's first nuclear reactor. In 1947, a personal position was created for Meitner at the University College of Stockholm with the salary of a professor and funding from the Council for Atomic Research.

Einstein himself respected Meitner and called her "our Marie Curie."

In 1944, Hahn received the Nobel Prize for Chemistry for the discovery of nuclear fission. Some historians who have documented the history of the discovery of nuclear fission believe Meitner should have been awarded the Nobel Prize with Hahn.

In 1966 Hahn, Fritz Strassmann and Meitner together were awarded the Enrico Fermi Award. On a visit to the USA in 1946 she received the honor of the "Woman of the Year" by the National Press Club dinner with President Harry Truman and others at the National Women's Press Club (USA) in January 1946, as well as many honorary doctorates and lectured at Princeton, Harvard and other US universities. Lise Meitner refused to move back to Germany, and enjoyed retirement and research in Stockholm until her late 80s. She received the Max Planck Medal of the German Physics Society in 1949. Meitner was nominated to receive the prize three times. An even rarer honour was given to her in 1997 when element 109 was named meitnerium in her honour. Meitner was elected a foreign member of the Royal Swedish Academy of Sciences in 1945, and had her status changed to that of a Swedish member in 1951.

After the war, Meitner, while acknowledging her own moral failing in staying in Germany from 1933 to 1938, was bitterly critical of Hahn and other German scientists who had collaborated with the Nazis and done nothing to protest against the crimes of Hitler's regime. Referring to the leading German scientist Werner Heisenberg, she said: "Heisenberg and many millions with him should be forced to see these camps and the martyred people." She wrote to Hahn:

"You all worked for Nazi Germany. And you tried to offer only a passive resistance. Certainly, to buy off your conscience you helped here and there a persecuted person, but millions of innocent human beings were allowed to be murdered without any kind of protest being uttered ... [it is said that] first you betrayed your friends, then your children in that you let them stake their lives on a criminal war – and finally that you betrayed Germany itself, because when the war was already quite hopeless, you did not once arm yourselves against the senseless destruction of Germany."

Meitner and Hahn were lifelong friends.

Meitner was of Jewish descent. The radio had begun to tell her what had been happening at places like Belsen and Buchenwald to the millions of Jews she had left behind. The tossing sleep Meitner had managed after learning of the concentration camp atrocities was plagued by nightmares. She had fits of uncontrollable weeping. She was in a mood to pour out her feelings, and her ensuing conversation with Moe Berg, Jewish descent, was probably a long one.

Meitner became a Swedish citizen in 1949. She moved to Britain in 1960 and died in Cambridge in 1968, shortly before her 90th birthday. As was her wish, she was buried in the village of Bramley in Hampshire, at St. James parish church, close to her younger brother Walter, who had died in 1964. Her nephew Otto Robert Frisch composed the inscription on her headstone. It reads "Lise Meitner: a physicist who never lost her humanity."