His debut on Broadway began when The Purple Road opened at the Liberty Theatre on April 7, 1913; he played the role of Bosco for the 136 performances before closing in August.

His next musical was an Al Jolson vehicle, Sigmund Romberg's Dancing Around, which opened at the Winter Garden Theatre on October 10, 1914, ran for 145 performances, and closed in the following February.

Later in 1915, Webb was cast in the all-star revue Ned Wayburn's Town Topics, which boasted 117 famous performers, including Will Rogers, as listed in the Century Theatre opening-night program for September 23, 1915.

In 1916, he had another short run with Cole Porter's comic opera See America First, which opened at the Maxine Elliott Theatre on March 28, 1916, and closed after 15 performances on April 8, 1916.

In the 1920s, Webb played in eight Broadway shows and made numerous other stage appearances, including vaudeville, and a handful of silent films.

Webb was busy with films, tours, and an appearance at the London Pavilion in 1921 as Mr. St. Louis in Fun of the Fayre and in 1922 in Phi-Phi – he did not return to Broadway until 1923.

In 1925, Webb appeared on stage in a dance act with vaudeville star and silent film actress Mary Hay.

Later that year, when her husband, Richard Barthelmess and she decided to produce and star the film New Toys, they chose Webb to be second lead.

Between 1913 and 1947, the tall, slender performer with the clear, gentle tenor appeared in 23 Broadway shows, starting with major supporting roles and quickly progressing to leads.

He introduced George and Ira Gershwin's "I've Got a Crush on You" in Treasure Girl in 1928; Arthur Schwartz and Howard Dietz's "I Guess I'll Have to Change My Plan" in The Little Show in 1929; "Louisiana Hayride" in Flying Colors in 1932; and Irving Berlin's “Easter Parade" in the very successful revue As Thousands Cheer.

Most of Webb's Broadway shows were musicals, but he also starred in Oscar Wilde's The Importance of Being Earnest, and his longtime friend Noël Coward's plays Blithe Spirit and Present Laughter.

Webb was in his mid-fifties when actor/director Otto Preminger chose him over the objections of 20th Century Fox chief Darryl F. Zanuck to play the elegant but evil radio columnist Waldo Lydecker, who is obsessed with Gene Tierney's character in the 1944 film noir Laura.

In the film Cheaper by the Dozen (1950), Webb and Myrna Loy played Frank and Lillian Gilbreth, real-life efficiency experts of the 1910s and 1920s, and the parents of 12 children.

It resulted in Webb's third hit in a row and led to exhibitors voting him the seventh biggest star in the United States.

Ewen Montagu in the true story of Operation Mincemeat, the elaborate plan to deceive the Axis powers about the Allied invasion of Sicily during World War II.

In Boy on a Dolphin (1957), second-billed to Alan Ladd, with third-billed Sophia Loren, he portrayed a wealthy sophisticate who enjoyed collecting illegally obtained Greek antiquities.

Fox was developing Journey to the Center of the Earth (1959) as a vehicle for Webb, but when he fell ill and was unable to work, James Mason stepped into the role.

[7] Webb's final film role was an initially sarcastic, but ultimately self-sacrificing Catholic priest in Leo McCarey's Satan Never Sleeps (1962).