Dietrich performs three musical numbers in this film, including the now-obscure "You Little So-and-So" (music and lyrics by Sam Coslow and Leo Robin) and "I Couldn't Be Annoyed" (music and lyrics by Leo Robin and Richard A. Whiting). The highlight is the infamous "Hot Voodoo" (music by Ralph Rainger, lyrics by Sam Coslow), which is nearly 8 minutes in length and mostly instrumental, featuring jazz trumpet and drums. Dietrich sings the lyrics toward the end of this sequence, which takes place in a nightclub.
The movie begins with seven American students traveling in Germany. They stop at a pond and spot six girls (who all work for a theater) bathing. The unclothed girls discover the male students and attempt to conceal themselves. One of the girls, Helen (Dietrich), asks them to go away, to which one of the young men, Ned (Marshall), responds by adamantly refusing to leave.
The movie shifts to years later, showing a mother bathing a boy, telling him to hurry since his father would be coming home soon. The mother and the boy turn out to be Ned's wife and son years after their first meeting at the pond. The scene cuts to a doctor's office, where we see a man offering to sell his body to science for money. The man is Ned, now an American chemist poisoned with radium and expecting to die within the year. The doctor tells him that there is a famous German physician who has had success treating radiation poisoning and recommends Ned to travel to Germany. It would cost him approximately $1500 and he would have to be there for six months.
The scene reverts to Helen and Ned putting their son, Johnny to bed after his bath. Johnny asks his parents to tell him the "Germany story", an ongoing bedtime tradition telling how Ned and Helen met. Ned recites this bedtime story by recalling his travel in Germany as a student and his encounter of "six beautiful princesses at a pond," one of whom told Ned that she will grant him a wish if he leaves. Ned wished to see her again, and that very night, Ned went to the local theater, finding the "princess" on the stage. Johnny asks his mother what the princess thought of Ned, to which she simply responds that she wanted to see him again. After the show, Ned asked "the princess" for a walk, and while under a tree, embraced her. Johnny insists on hearing, "and then what happened?" after their first kiss, to which Ned replies with a Cheshire grin, "and then..we started to think of you.."
With Johnny asleep, Ned and Helen discuss the possibility of having Ned travel to Germany for the treatment. It is very evident that Ned loves Helen and wishes not to leave her, and at the same time, Helen exhibits her undying love for Ned by insisting that she return to theater work to help finance his trip. Although Ned is against this, Helen finds work at a night club and befriends a fellow cabaret girl "Taxi" who is of obvious lower class than Helen. She tells Helen about Nick Townsend (Cary Grant) a famous millionaire politician who is a regular at the club and who gave her expensive jewelry for "favors."
Helen attracts great attention in her first performance "Hot VooDoo" (in which she is required to don an ape suit and remove the costume head dramatically). Nick Townsend, who is in the audience, is interested in Helen, and after the show, goes back stage to meet her. He found out about her family troubles and gives Helen a check for $300 as down-payment for her husband's medical treatment.
Eventually Helen accumulates enough money to fund Ned's treatment. She lies to Ned about how she got the money, saying that the producer "paid her in advance." Out of apparent guilt for lying to him, she then asks if Ned "loves her," to which he replies, "Do I love you? Oh you silly little thing." He then embraces her. The next day, Johnny and Helen see Ned off to Germany at the ship docks.
Nick shows up to give Helen a ride home when the ship sails, much to her surprise and irritation. Nick then said he had a "friend with an apartment" in which she and Johnny can stay all summer, thereby sparing her from working again. Nick takes the liberty to call Helen's business manager to informs him that Helen can quit immediately because she has no contract with him. Helen begins to live at Nick's "friend's apartment" and eventually develops feelings for Nick. When she discovers that her husband is returning from Germany she realizes how much she is indeed attracted to Nick and finally admits that she loves him. However, she informs Nick that she must go back to Ned, with the reason being that he isn't "as strong" as Nick and therefore he needs her more than Nick does.
Before Ned is to return to the States, Helen goes on a two-week vacation with Nick, with both believing that it would be their final private time together. Meanwhile, Ned returns two days early, finding his home empty with neighbors informing him that they haven't seen Helen nor Johnny for two weeks. Ned ultimately finds out that his wife has quit her job and been keeping company with Nick. Helen returns home from her vacation with Nick and bids him farewell. (Nick informs Helen he would travel to Europe to "forget about you.") Upon returning home, Helen is dismayed to discover Ned is already there, and that she had failed to see a telegram warning of his early arrival because she was with Nick.
Helen implies her act of infidelity to Ned saying that she has been "untrue" to him, had lied about the money and said it was the only way to get him his treatment. Ned is very angry and tells her he is going to pay her money back and states that he wishes he had never met her. He banishes Helen from the house and threatens to take her to court for custody of Johnny. He demands that she bring Johnny into the room so they could reveal the plans of their separation to him. Helen agrees, but grabs Johnny and escapes. They both end up living on the run. Ned reports his wife's and son's disappearance to the police, and they begin to track her.
Helen and Johnny end up renting an apartment where she befriends a Black housekeeper (Hattie McDaniel, uncredited) who senses "some man outside" is a detective. The detective starts a conversation with Helen telling her about his problematic chase, (ironically, for her) and even has a beer with her. Helen takes him to her room and eventually Johnny pops into the room, revealing his and his mother's identities to the detective. Helen voluntarily turns herself in. They take the train back to Ned and home.
Helen realizes that life on the lam is not conducive to raising a child correctly and agrees to return Johnny to Ned. Ned asks her to never see him or Johnny again. After a dramatic emotional breakdown, Helen throws herself into a work-a-holic mode: singing in cabarets, making a successful career which eventually catapulted her to Paris. In a fateful performance, she runs into Nick, who continues to profess his feelings for Helen. Nick knows that Helen loves Johnny and that she wishes to be with her son again. Nick offers to take her back to the U.S., and the two return engaged to be married. Helen comes home and sees her son, Johnny, who is unaware of his mother's engagement to Nick.
Johnny asks his mother to tell him the "Germany story" again in front of Ned, since Ned had refused to tell it (because he "had forgotten it"). Johnny then proceeds to tell the story himself, encouraging his parents to join in the dialogue. Through this forced dialogue with Johnny telling the story, Ned and Helen become aware how their separation affects Johnny, who wishes to remain in a world in which his parents are together.
Helen then sings to Johnny the song that she sang before he sleeps every night (the lyric of this song is a poem by Heinrich Heine). During the song, the audience sees a close-up of the music-playing carousel, a ceramic music box merry-go-round that we see at the beginning of the film with the first bed-time story. This is a symbol of their up and down, round and round life and is an important prop in creating a poignant moment wherein Helen and Ned realize that their home is where they both ultimately belong.
Blonde Venus received a mixed to positive reception upon release. Mordaunt Hall of The New York Times called it "muddled, unimaginative and generally hapless piece of work, relieved somewhat by the talent and charm of the German actress [Dietrich] and Herbert Marshall's valiant work in a thankless role". Jose Rodriguez of Script remarked that the theme is as "old as life, and almost as interesting", praising the "force" and "instinctive cunning" of the director. Forsythe Hardy of Cinema Quarterly gave the film a gushing review, calling the picture "more brilliantly polished than any other America has sent us this year". He particularly praised the cinematography, writing: "For an hour the screen is filled with a succession of lovely images—finely assembled detail and imaginatively composed settings, photographed with a camera unusually sensitive".