The troupe didn't ride in regular trains, they travelled in three custom-built, lavishly decorated private railroad cars which allowed Field to move 50 performers, musicians and other staff, paired with tons of scenery across the United States easily. Murray was documented in the official roster for the 1902-3 season advertised as "William Murray, The Eccentric Singing and Dancing Comedian". Shortly thereafter, Al G. Field intervened, telling Murray that "William" sounded much too stiff, formal and operatic, insisting on "Billy Murray" instead, arguing that it sounded more accessible, punchy and perfect for a fast-talking comedian. Field's intuition was correct, and Murray's popularity exploded, with theatregoers across America recognising his name. It was under Field that Murray perfected his breath control, as he was expected to participate in demanding clog dancing whilst simultaneously singing comic numbers. These physical demands built the exceptional lung capacity and breathless phrasing that came to define much of his future career. 

In May 1903, Murray arrived in the New York area. Initially, he refused to sign with a single label, instead working as a freelancer amongst multiple different labels, the National Phonograph Company (a company run by Thomas Edison), the Victor Talking Machine Company and Columbia. He would frequently record the same songs for different labels in the span of a few days. His first commercial solo cylinder came in August with Edison, I'm Thinking of You All of de While and Alec Busby, Don't Go Away. Later that year, he recorded Tessie (You Are the Only, Only, Only). When the Boston Americans played the Pittsburgh Pirates in the 1903 World Series, Boston fans changed the lyrics to mock Pittsburgh players, and the song became baseball's first unofficial anthem in America, which propelled this to become his first of 169 chart hits. 

Because exclusive artist contracts were not standard practice at the time, Murray did not allow himself to be tied to one individual label. When a song became a hit in Tin Pan Alley, Murray would record it for one company in the morning, then travel across the city to record for another and record it for a third a day later. Unlike his peers, who often had primary careers on stage performing in vaudeville shows, Murray focused a vast majority of his efforts on his studio recordings, mastering song basics before his first takes, and made most of his living from the accumulation of recording session fees. 

By 1904, he had established himself as the primary interpreter of Tin Pan Alley hits, but his fame was only just beginning to grow. Because of the nature of acoustical recordings, Murray was in a unique position, as his powerful lungs and sharp enunciation meant his words would never sound slurred or muffled in the wax recording. Murray was a master of ethnic dialects, comedy routines and coon songs (the era's term for syncopated, ragtime-influenced novelty songs). He developed a technique of singing absurd or comedic lyrics in an intentionally flat, deadpan tone, realising that an inexpressive delivery would make punchlines much funnier for a listener. 

Around Mid-1905, he was dubbed "The Denver Nightingale" by Samuel Rous, Catalog Manager at Victor. In August of that same year, he recorded In My Merry Oldsmobile, which spurred on a wave of songs related to the blossoming automotive industry. However, it was in October of 1906 that he realised the vast power of collaboration, partnering with Ada Jones. 

In his tracks with Jones, the two had a kind of witty, romantic "boy-and-girl" banter which instantly became popular, and the two had generated 44 chart hits before the decade ended. 

He also began to lend his voice to prominent vocal groups, working alongside the Haydn Quartet whilst also laying the groundwork for the American Quartet which was formed in 1909 specifically to back him on major tracks, for example By the Light of the Silvery Moon. 

It was also in 1909 that his freelance lifestyle came to an unglamorous end. Two of the giants in the talking machine industry, namely Victor and Edison, locked him into a joint 10-year exclusive contract, legally prohibiting him from continuing to freelancing. He was only allowed to record disc records for Victor and cylinder records for Edison. This offered them a monopoly on his work, and they utilised this by shifting him to group recordings. He was paired with The American Quartet. This comprised him as the second tenor, John Bieling as the first tenor, Steve Porter as the baritone and William F. Hooley as the bass. The Quartet achieved over 50 charted hits and 6 Number 1 records, including the First World War anthem Over There.

The 1910s also saw him introduce some of the biggest standards in American pop history, including Irving Berlin's Alexander's Ragtime Band and continued to duet with Ada Jones. 

Unlike most other artists of the day, Murray did not tour the traditional vaudeville circuit. It was only in 1917 that he hit the road as part of the "Eight Popular Victor Artists", a hand picked troupe of Victor's top recording stars comprised of Murray, Henry Burr, Albert Campbell, John H. Meyer, Frank Croxton, Monroe Silver, Rudy Wiedoeft and Frank Banta. He toured the United States alongside them performing live to allow him to promote the sale of Victor phonograph players. They traveled by train to opera houses across North America. A typical show involved the artists standing alonsgide a Victor Victrola phonograph player, and they would start singing a song live before stopping mid-verse to let the record player take over. The idea was to challenge audiences to see if they could tell the difference between the live human voice and the acoustic machine. He was often the comedic highlight of the evening, with Newspaper reviews noting that whilst Henry Burr would sing the serious ballads, Murray would bounce onto the stage to perform rapid-fire patter songs, intentionally breakingh the formal, stuffy atmosphere that accompanied concert halls.

On January 28, 1927, Murray was called into the studio to sing a vocal refrain for I'm Looking Over a Four Leaf Clover alongside Jean Goldkette's Orchestra. Goldkette's pianist, Irving Riskin, remarked that Murray looked and felt completely out of place in the studio. Murray was the disciplined, old-school professional who felt much more comfortable following the sheet music strictly, whereas Beiderbecke and other jazz musicians present were drinking, improvising and playing wild, modern syncopations. 

The final blow he faced in the 1920s came directly from Wall Street. In 1927, the founding management of Victor sold the company to a syndicate of banking houses which eventually merged into RCA. These new corporate owners restructured the label's talent roster and they saw little reason to keep paying premium, high-salaried retainers to stars of the pre-war acoustic era. When Murray's contract ended in 1928, Victor did not renew it. He was forced back into freelance, in a landscape which was no longer suited to him, but he managed to find success. Murray found success with minor, lower-budget labels like Banner, Cameo, Harmony and Brunswick who utilised cheaper, less sensitive electrical equipment from Marsh and Brunswick-Balke-Collender, meaning they gladly hired him because his loud, unamplified voice could still track very well on their older equipment. 

However, where most artists would see their decline, Murray was offered a new chance of life. In 1929, as record sales began to collapse due to the Wall Street Crash, he teamed up with fellow recording artist Walter Van Brunt. The two of them voiced a historic sound-on-film instructional cartoon produced by Western Electric titled Finding His Voice in Fleischer Studios.  This single role laid the groundwork for his 1930s career, introducing his voice to Hollywood animation and saving him from complete irrelevance at the beginning of the Great Depression. 

Murray officially retired in 1944, following a heart attack. His retirement was spurred on by a diagnosis of myocardial heart disease, with his doctor ordering him to cease with travelling, radio broadcasts, studio work and the travel that accompanied them due to the exertion it had on his body. In spite of this, he continued to receive offers for appearances and comebacks however none of these were fulfilled.

He settled in his long-time home of Freeport, Long Island to live with his wife, Madeleine. His first two marriages had ended in divorce, and he had no biological children. Freeport was once a colony for theatrical professionals, actors and vaudevillians where Murray's background was respected despite the declining community. Murray was by no means wealthy, as the industry standard of the time focused heavily on session fees rather than royalties. It was Murray's investments during the boom of the 1920s and income he earned in the 1930s. Whilst his retirement was not lavish, he enjoyed a middle class budget and lived very comfortably in a home he owned outright.

After the Second World War, American pop culture experienced a temporary wave of early-20th-century nostalgia and producers from the first commercial television networks such as CBS or NBC began to seek out living legends from that time. Between 1948 and 1950, Murray received formal letters and phone inquiries from people representing Ed Sullivan and Arthur Godfrey who wanted him to appear as a guest star to sing some of his old hits. Murray was flattered by these requests, but was unyielding due to his physical limitations, and his heart condition meant that he could not handle the stress that live television would bring, whether it be performing, travel or the rehearsals required for it. Because of this, every offer he received was ultimately turned down. 

In 1948, Columbia Records introduced LP vinyl records, which was the nail in the coffin for 78rpm acoustic shellac discs which were still selling in commercial stores. Because Murray's entire catalog was recorded on these shellac discs, it was not compatible with the new market which began to emerge by 1950, and the public consequently forgot about who he was, turning him into a regular, anonymous face in Long Island. 

By 1950, Murray had become almost completely anonymised. People in his neighbourhood would not have known him as the man who sold around 300 million records, but rather as William Murray, a friendly, polite, elderly neighbour who lived quietly with his wife, Madeleine. However, it was also around this time that Murray was engaged by Jim Walsh, a writer for Hobbies magazine who was documenting the history of early recording artists. Due to his sharp memory, he spent a lot of his time between 1950 and 1954 replying to letters from Walsh and a collector named Quentin Riggs, providing details about forgotten studio sessions, identifying pseudonyms he used and recounting days working alongside famous names such as Edison and Sousa, which would have been lost to time.