In Moonstone, Colorado, Doctor Archie helps Mrs. Kronborg give birth to her son, Thor. He takes care of their daughter, Thea, who is sick with pneumonia. The next year, she goes to the Kohlers for piano lessons with Wunsch, and practices daily for two hours or four hours, depending if school is in session or not. The doctor goes to Spanish Johnny who is sick. Later, Ray Kennedy goes out to the countryside with Johnny, his wife, Thea, Axel, and Gunner. Although she is only twelve and he is thirty, he dreams of marrying her when she is old enough. They tell stories of striking it rich in silver mines in the west.
Before Christmas, Thea plays the piano at a concert, but the town paper praises her rival Lily which upsets Thea, as she wanted to sing rather than perform an instrumental piece. Tillie turns down the local drama club's notion to have Thea play a part in The Drummer Boy of Shiloh , knowing that acting is not her niece's talent. After Christmas, Wunsch tells Thea about a Spanish opera singer who could sing an alto part of Christoph Willibald Gluck. She sings for him. He says she needs to learn German for many of the good songs. Wunsch gets so drunk that he behaves badly and hurts himself. Ten days later, all of his students discontinue their lessons with him, and he leaves the town. Shortly after, Thea drops out of school and takes up his students; at fifteen she begins to work full-time.
Thea and her mother enjoy a trip to Denver on Ray's freight train, riding in the caboose. They stop for lunch with the station agent at a town along the way. That fall, Mr. Kronborg insists that Thea help at the Wednesday prayer meeting by playing the organ and leading the hymns, and she does. At fifteen, religion perplexes Thea, as typhoid kills her schoolmates and a local tramp, source of the infection, is made to leave town; she wonders if the Bible tells people to help him instead. Dr. Archie tells her that people have to look after themselves. On the way from Moonstone to Saxony, Ray's train has an accident and the next day he bids an emotional goodbye to Thea before he dies. After the funeral, Dr. Archie informs Mr. Kronborg that Ray has bequeathed six hundred dollars to Thea for her to go to Chicago and study music there. Her father agrees to let her go despite her only being seventeen.
In Chicago, Thea settles close to the parish of a Swedish Reformed Church with two German women; she sings in the choir and in funerals for a stipend, and takes piano lessons with Mr. Harsanyi. When Mr. Harsanyi learns Thea sings in a church choir, he asks her to sing. He is very impressed by her voice. Later, he meets with the conductor of the Chicago Orchestra and asks him who is the best voice teacher in the area; it is Madison Bowers. He then parts with Thea, explaining that her voice is her true artistic gift, not her playing. After several weeks of singing lessons, she takes a train back to Moonstone for her summer vacation. She has grown. She goes to a Mexican ball with Spanish Johnny and sings for them, feeling the pleasure of the audience for the first time. Back in her house, Anna reproaches her for singing for them and not their father's church. She returns to Chicago in fall.
In Chicago, Thea moves from one home to another. She takes daily singing lessons, spending the afternoons as accompanist for Bowers more accomplished students. She grows tired of them, not all people like the warm and intelligent Hafsanyis. Fred Ottenburg shows up for lessons, a man who is educated, lively and closer to her age than all her male teachers. He introduces her to the Nathanmeyers, a family who loves operatic music and her style of singing. They invite her to sing at their musical evenings, helping her with proper dress. Thea catches an infection and does not fully recover; she needs a break in her familiar desert setting but will not return to her family until she has accomplished something. Fred suggests that she spend the summer on a ranch in Arizona with some of cliff homes of the ancient peoples that Thea has longed to see.
Thea gets off the train at Flagstaff, Arizona, seeing the San Francisco Peaks to reach the Bitmer home. She recoups her health, with days in the canyon, resting in one of the ancient cliff dwellings, while sharing the meals of Mr. and Mrs. Bitmer. She comes to know herself better in the moments of isolation. Ottenburg joins her in July. After much direct conversation, they kiss. They take refuge from a severe storm, and then make a daring trek back to the ranch in the dark, met by Bitmer with a lantern. They talk of what is next; Thea thinks she is in love and considers marrying him. Fred suggests a visit to Mexico City, before getting her to Germany, where he feels she belongs, for her singing. Ottenburg does not tell her he married eight years earlier, though he and his wife have been estranged for most of those years, keeping up appearances.
In Denver, Dr. Archie receives a telegram from Thea summoning him to New York City and asking him to lend her money so that she can study singing in Germany. Fred told Thea about his marriage in Mexico City, and Thea accepts it, but makes it clear the limits his first marriage imposes on them. She tells Archie about this. In New York she tells Fred that she will leave and will not accept his financial help. Archie goes to dinner with Ottenburg and Thea. The next day, Fred leaves to tend his dying mother. Thea ponders the risks of her ambition, realizes she is young, just 20, and heads to Germany.
Ten years after Thea leaves for Germany, Dr. Archie lives in Denver after his mining investments succeed and his wife has died. His life is better. He was involved in politics but is now tired of it. He wants to go to New York City, as does Fred, where Thea is performing. He has not seen her in ten years. Four years after she left for Germany, Thea's father died of disease and Mrs. Kronborg began to fail without him. Thea ached to go home to her mother, but opportunity opened in the opera company in Dresden for her before she can go home. Dr. Archie tries to keep Mrs. Kronborg's spirits up, but she dies. Thea has paid back the loan to Dr. Archie already.
In New York City, Thea performs at the Metropolitan Opera House. Dr. Archie and Fred are there to attend her performance. The three are good friends. Fred is still tied to his wife, who went mad and lives in an asylum these seven years; but he pines to raise a son. Thea is asked to replace an ill singer at the last minute, and she performs very well. Thea is then announced to sing the entire role of Sieglinde , in the program. This role is well-suited to her voice. Besides Archie and Fred, two other people from her past are in the audience— Harsanyi, her teacher from Chicago, and Spanish Johnny, the Mexican mandolin player from Moonstone, who all deeply enjoy her performance, as does the entire audience. In the epilog, Tillie Kronborg is in Moonstone, enjoying her niece's successes in the opera. She recalls hearing the famous Kronborg when the opera travelled to Kansas City, and she is happy.