[4] St. Luke's was established in October 1903 by American Episcopalian missionaries as a charity ward and dispensary hospital led by retired bishop Charles Henry Brent.

It was founded as the Dispensary of St. Luke the Beloved Physician, a fully free outpatient clinic for the poor in Calle Magdalena (now Masangkay Street) in Tondo, Manila.

[5] In 1961, the health facility would move to its current location in Quezon City.

[6] The St. Luke's Medical Center in Quezon City is the first hospital in the Philippines and the second one in Asia to be accredited by the Joint Commission International.

The hospital first earned the distinction in 2003 and the accreditation has been renewed at least four times[7] In 2013, German based accreditation organization, TEMOS gave an Excellence in Medical Tourism and Quality in International Patient Care certificate to the hospital in Quezon City.