Romance and career collide when ace news reporter Hildy Johnson tries to leave her job and her editor/ex-husband Walter Burns, for a quiet life of wedded bliss. On her way out the door, Burns convinces her to tackle one last assignment—a controversial execution scheduled for the next morning—which is certain to be the greatest story of her career. Burns tries to keep Hildy busy while he thinks up ways to stop her impending marriage to the dull but respectable Bruce Baldwin. Meanwhile, Hildy finds herself aiding an escaped prisoner and uncovering a major political scandal.

Rosalind Russell was insecure during the first days of filming His Girl Friday, knowing that she had been far down on the list of choices for the female lead. Making matters worse was the fact that director Howard Hawks had just watched her initial scenes with Cary Grant without making any comment. Finally, she expressed her frustration to Grant, who counseled, "If he didn't like it, he'd tell you." When she asked Hawks how he felt about her work, he said, "You just keep pushin' him around the way you're doing." That was enough to put her at ease.

To maintain the film’s trademark fast pace, Hawks encouraged his cast to add dialogue and funny bits of business and step on each other's lines whenever possible. Russell planned some of her "ad-libs." Concerned about the film's potential, she hired a writer from her brother's advertising firm to create some witty one-liners for her. She paid the man $200 a week on her own and never told Hawks about it. Grant caught on, however, and would ask her each morning, "What have you got today?"

To capture the film's fast-paced dialogue clearly, Hawks decided to use multiple microphones rather than one overhead boom microphone. Since the microphones couldn't be turned on simultaneously, a sound technician had to switch from mic to mic on cue. Some scenes required as many as 35 switches. With all of the improvisation during shooting, cameraman Joseph Walker had a hard time keeping up. He had a particular problem shooting Russell in a flattering manner, since he never knew exactly where she was going to be. Careful lighting was required to make sure the actress’s jowls didn’t appear unflattering on screen. Finally, he got her makeup man to paint a dark shadow along her jaw line, effectively fixing the situation.

One scene required Grant to push Russell onto a couch. Hawks asked the actor to try shoving her harder. When Grant protested that he didn't want to kill her, Hawks said, "Try killin' 'er." That spirit translated to the film’s marketing. The film's tagline was "They're at each other's throats—when they're not in each other's arms.

His Girl Friday finished shooting on November 21, 1939, seven days behind schedule. The delays were caused by the complexity of shooting the rapid-fire dialogue, which had to be carefully timed with business and movement. The restaurant scene in which Burns takes Hildy and Bruce to lunch took four days to shoot; the original schedule had only allotted two days for the scene.