• Alexander Knox as Woodrow Wilson
• Charles Coburn as Professor Henry Holmes
• Geraldine Fitzgerald as Edith Wilson
• Thomas Mitchell as Joseph Tumulty
• Ruth Nelson as Ellen Wilson
• Sir Cedric Hardwicke as Senator Henry Cabot Lodge
• Vincent Price as William G. McAdoo
• William Eythe as George Felton
• Mary Anderson as Eleanor Wilson
• Ruth Ford as Margaret Wilson
• Sidney Blackmer as Josephus Daniels
• Madeleine Forbes as Jessie Wilson
• Stanley Ridges as Admiral Grayson
• Eddie Foy Jr. as Eddie Foy
• Charles Halton as Colonel House
• Thurston Hall as Senator E.H. Jones
• J. M. Kerrigan as Edward Sullivan
• James Rennie as Jim Beeker
• Katherine Locke as Helen Bones
• Stanley Logan as Robert Lansing
• Marcel Dalio as Georges Clemenceau
• Edwin Maxwell as William Jennings Bryan
• Clifford Brooke as David Lloyd George
• Tonio Selwart as Count Johann Heinrich von Bernstorff
• John Ince as Senator Watson
• Charles Miller as Senator Bromfield
• Francis X. Bushman as Bernard Baruch (uncredited)
• Davison Clark as Champ Clark (uncredited)
• Eula Morgan as Singer (uncredited)
• Jess Lee Brooks as Simms, Georgia-born White House servant who welcomes ex-neighbor Ellen Wilson (uncredited)

Wilson was initially intended as a historical drama about a fictional American family living during the Progressive Era before being rewritten by Lamar Trotti into a biopic about Woodrow Wilson. Wilson's daughter, Eleanor Wilson McAdoo, served as an informal counselor. Journalist Ray Stannard Baker, an authority on Wilson, served as an adviser.
Before Knox was cast as Wilson, Ronald Colman and Frank Conroy were considered. Claudette Colbert was also considered for one of Wilson's wives. Dwight Frye was cast as Secretary of War Newton D. Baker but died of a heart attack on November 7, 1943, a few days prior to his filming start. Ernest Palmer was hired as cinematographer but had to be replaced by Leon Shamroy after falling ill, while James Basevi quit as art director due to disagreements with the rest of the crew.
With a budget of $5.2 million, Wilson was the most expensive film produced by Fox at that time. Much of the budget went to constructing accurate and detailed sets for White House locations such as the East Room, the Blue Room, the Oval Office and the Lincoln Bedroom. Scenes of the Democratic National Convention were shot at Shrine Auditorium in Los Angeles while scenes set at Princeton were shot on-location in Trenton, New Jersey. Other scenes were shot at the Biltmore Theater in Los Angeles; Pueblo, Colorado; and Midwick Country Club in Alhambra, California.

Wilson was promoted by the NBC Blue Network radio show Hall of Fame Broadcast with a radio adaptation of sections of the script.

Wilson reportedly lost $2 million for Fox. Ticket sales were damaged due to the United States Department of War prohibiting the film's exhibition on Armed Forces bases during World War II under provisions of the Soldier Voting Act against the screening of political material that could influence elections such as the ones about to be held on November 7, 1944.
The film received generally positive reviews but was not without its detractors. The New Republic film critic Manny Farber was particularly unenthusiastic, calling the production "costly, tedious and impotent" while writing: "The effect of the movie is similar to the one produced by the sterile post-card albums you buy in railroad stations, which unfold like accordions and show you the points of interest in the city ... The producers must have known far more about the World War, the peace-making at Versailles, and Wilson himself, but that is kept out of the movie in the same way that slum sections are kept out of post-card albums ... About three-quarters of the way through, a large amount of actual newsreel from the first World War is run off and the strength of it makes the film that comes before and after seem comical."

President Franklin D. Roosevelt, a protege of Wilson's, screened the film for guests at the Second Quebec Conference in 1944. British Prime Minister Winston Churchill, however, was no fan. He excused himself in the middle of the film and went to bed.
Despite the negative press and lackluster commercial performance, the film received ten nominations at the 17th Academy Awards, winning five:
• Best Art Direction-Interior Decoration, Color (Wiard Ihnen and Thomas Little)
• Best Cinematography, Color (Leon Shamroy)
• Best Film Editing (Barbara McLean)
• Best Sound, Recording (E. H. Hansen)
• Best Writing, Original Screenplay (Lamar Trotti)
Wilson was also nominated for:
• Best Picture (Darryl F. Zanuck)
• Best Director (Henry King)
• Best Actor in a Leading Role (Alexander Knox)
• Best Music, Scoring of a Dramatic or Comedy Picture (Alfred Newman)
• Best Effects, Special Effects (Fred Sersen and Roger Heman Sr.)