Saya Thetgyi was born in the farming village of Pyawbwegyi, eight miles south of Rangoon.
He ordained as a bhikkhu (monk) for some time. At the age of 23, he learned Anapana meditation from a lay teacher, Saya Nyunt. When a cholera epidemic struck the village in 1903, many died, including U Thet's son and young teenage daughter. This calamity affected U Thet deeply, and not finding refuge anywhere he asked permission from his wife and sister-in-law, Ma Yin, to leave the village in search of "the deathless."

Accompanied in his wanderings by a devoted companion and follower, U Nyo, U Thet wandered all over Burma in a fervent search, visiting mountain retreats and forest monasteries, studying with different teachers, both monks and laymen. Finally he went north to Monywa to learn Vipassana from the Venerable Ledi Sayadaw. He returned to his village after a few years and started teaching Anapana in 1914.

In about 1915, after teaching for a year, U Thet took his wife and her sister to pay respects to Ledi Sayadaw who was then about 70 years old. When U Thet told his teacher about his meditation experiences and the courses he had been offering, Ledi Sayadaw was very pleased

It was during this visit that Ven. Ledi Sayadaw gave his walking staff to U Thet, saying:

"Here my great pupil, take my staff and forward. Keep it well. I do not give this to you to make you live long, but as a reward, so that there will be no mishaps in your life. You have been successful. From today onwards you must teach the Dhamma of rupa and nama (mind and matter) to 6,000 people. The Dhamma known by you is inexhaustible, so propagate the sasana (era of the Buddha's teaching). Pay homage to the sasana in my stead.

The next day Ledi Sayadaw summoned all the monks of his monastery. He requested U Thet to stay on for 10 or 15 days to instruct them. The Sayadaw then told the gathering bhikkhus:

"Take note, all of you. This layman is my great pupil U Po Thet, from lower Burma. He is capable of teaching meditation like me. Those of you who wish to practice meditation, follow him. Learn the technique from him and practice. You, Dayaka Thet (a lay supporter of a monk who undertakes to supply his needs such as food, robes, medicine, etc.), hoist the victory banner of Dhamma in place of me, starting at my monastery."

U Thet then taught Vipassana meditation to about 25 monks learned in the scriptures. It was at this time that he became known as Saya Thetgyyi (saya means "teacher"; gyi is a suffix denoting respect).

Saya Thetgyi was the first lay teacher of Vipassana since the time of the Buddha. For 30 years he taught meditation to all who came to him, guided by his own experience and using Ledi Sayadaw's manuals as a reference. The village was not far from Rangoon, the capital of Burma under the British, so government employees and city dwellers like Sayagyi U Ba Khin , also came. By 1945, when he was 72, he had fulfilled his mission of teaching thousands.