Already planning to become a doctor, at the age of sixteen he began a Bachelor of Science (BSc) course at University College, Cardiff, graduating three years later with first class honours.

In 1902 he entered University College Hospital (UCH) in London to train as a doctor, graduating MBBS with the gold medal in 1905.

From 1906, he corresponded with the Dutch physiologist Willem Einthoven concerning the latter's invention of the string galvanometer and electrocardiography, and Lewis pioneered its use in clinical settings.

In that year, Thomas Lewis and Arthur MacNalty (later the Chief Medical Officer of the United Kingdom) employed electrocardiography to diagnose heart block.

[15] He directed a study of the condition known as "soldier's heart" and, having established it was not a cardiological problem, renamed it the "effort syndrome".

[17] After the war, Lewis established the clinical research department at UCH and continued his work on cardiac arrhythmia.

Lewis suffered a myocardial infarction at the age of 45 and gave up his 70-cigarette-a-day habit, being one of the first to realise that smoking damaged the blood vessels.