Spanning six decades, it tells the story of Father Francis Chisholm, an unconventional Scottish Catholic priest who struggles to establish a mission in China.

Beset by tragedy in his youth, as a missionary Chisholm endures many years of hardship, punctuated by famine, plague and war in the Chinese province to which he is assigned.

Through a life guided by compassion and tolerance, Chisholm earns the respect of the Chinese—and of fellow clergy who would mistrust him—with his kindly, high-minded and courageous ways.

After the father is beaten by an anti-Catholic mob, Chisholm's mother tries to lead him home to safety, only for them both to drown after falling off a bridge into a strong current, leaving young Francis an orphan.

When the attempt fails, Willie's father contacts Aunt Polly, who takes Francis home to live with her and her daughter, Nora.

At his second appointment, a local girl claims to have come across a previously dry well that had now burst forth anew with healing properties, accompanied by visions of the Blessed Virgin Mary, drawing comparisons to Saint Bernadette.

Much of this section deals with the superficial and detrimental aspects of the mission systems, which focus only on official numbers and not on improving spiritual lives.

When a flood hits and destroys the mission, the lead nun, astonished by Chisholm's moral quality, seeks assistance from her brother, a rich German, to rebuild it.

The book was made into a 1944 film The Keys of the Kingdom starring Gregory Peck as Father Francis Chisholm and Vincent Price as Anselm "Angus" Mealey.