Morecambe and Wise's partnership began in 1941 when they were each booked separately to appear in Jack Hylton's revue, Youth Takes a Bow. War service broke up the act but they reunited by chance in 1946 when they joined forces again. Initially appearing in music hall, they made their name in radio, transferring to television in 1954.

Their show, Running Wild, was not well received and led to a damning newspaper review: "Definition of the week: TV set, the box in which they buried Morecambe and Wise." Eric apparently carried this review around with him ever after and from then on Eric and Ernie kept a tight control over their material. In 1956 they were offered a spot in the Winifred Atwell show with material written by Johnny Speight and this was a success.

They had a series of shows that spanned over twenty years, during which time they developed and honed their act, most notably with the original move to the BBC in 1968 where they were to be teamed with their long-term writer Eddie Braben and it is this period of their careers that is widely regarded as their "glory days". Their shows were:-

- Two Of A Kind (1961) (ATV, 1961-1968. Writers: Dick Hills and Sid Green).
- The Morecambe & Wise Show (1968) (BBC, 1968-1978. Writers: Hills and Green for one series and thereafter Eddie Braben).
- The Morecambe & Wise Show (1978) (Thames Television, 1978 until their final show together at Christmas 1983. Writers: themselves, Barry Cryer, John Junkin, and from 1980, Eddie Braben).

During the 1960s the pair starred in three unsuccessful feature films (The Intelligence Men (1965), That Riviera Touch (1966), and The Magnificent Two (1967)). In 1983 they made their last film, Night Train To Murder. In 1976, they were both awarded the OBE.

A typical Morecambe and Wise show was effectively a sketch show crossed with a sitcom, although shows could also include the duo appearing "as themselves" on a mock stage in front of curtains emblazoned with an M and W logo (this was usually to open the show). Morecambe and Wise’s comic style varied subtly throughout their career, depending on their writers.

Their original writers Dick Hills and Sid Green took a relatively straightforward approach, depicting "Eric" as an aggressive, knockabout comedian and "Ernie" as an essentially conventional and somewhat disapproving straight man. When Eddie Braben took over as writer, he made the relationship considerably deeper and more complex.

The critic Kenneth Tynan noted that, with Braben as writer, Morecambe and Wise had a unique dynamic, Ernie was a comedian who wasn’t funny, while Eric was a straight man who was funny. The Ernie persona became simultaneously more egotistical and more naïve.

Morecambe pointed out that Braben wrote him as less hostile to Wise and more protective of him than he had been under Hills and Green. Wise's contribution to the humour is a subject of an ongoing debate. To the end of his life he would always reject interviewers' suggestions that he was 'the straight man', preferring to call himself 'the song-and-dance man'. However, Wise’s skill and dedication as the duo’s manager was essential to their joint success.

A central conceit was that the duo lived together as close, long-term friends (there were many references to a childhood friendship) who shared not merely a flat but also a bed -- although their relationship was purely platonic and merely continued a tradition of comic partners sleeping in the same bed that started with Laurel and Hardy.

Morecambe was initially uncomfortable with the bed-sharing sketches, but changed his mind upon being reminded of the Laurel-and-Hardy precedent; however, he still insisted on smoking his pipe in the bed scenes "for the masculinity". The front room of the flat and also the bedroom were used frequently throughout the show episodes, although Braben would also transplant the duo into various external situations, such as a health-food shop or a bank. Many references were made to Ernie's supposed meanness with money and drink.

Another conceit of the shows during the 'Braben era' was Ernie's utterly confident presentation of amateurishly inept plays. This allowed for another kind of sketch: the staged 'historical drama', which usually parodied genuine historical television plays or films (such as Stalag 54, Antony and Cleopatra, or Napoleon and Josephine). Wise's character would write a play, complete with cheap props and appallingly clumsy writing ("the play what I wrote" became a catchphrase), which would then be acted out by Morecambe, Wise and the show's guest star.

Guests who participated included many big names of the 1970s and 80s, such as Flora Robson, Penelope Keith, Laurence Olivier, John Mills, Vanessa Redgrave, Eric Porter, Peter Cushing and Frank Finlay - as well as Glenda Jackson (as Cleopatra: "All men are fools. And what makes them so is having beauty like what I have got..."). Jackson had not previously been known as a comedienne and this appearance led to her Oscar winning role in A Touch of Class. Morecambe and Wise would often pretend not to have heard of their guest, or would appear to confuse them with someone else (former UK Prime Minister Harold Wilson returned the favour, when appearing as a guest at the duo's 'flat', by referring to Morecambe as 'Mor-e-cam-by').

Also noteworthy was the occasion when the respected BBC newsreader Angela Rippon was induced to show her shapely legs in a dance-number (she had trained as a ballet dancer before she became a journalist and TV presenter), and when Richard Greene of Robin Hood fame played a lost aviator called 'Miles Behind'. Braben later said that a large amount of the duo's humour was based on irreverence. A running gag in a number of shows was a short sequence showing a well-known artist in closeup saying "I appeared in an Ernie Wise play, and look what happened to me!".

The camera would then pull back and show the artist doing some low-status job such as selling newspapers, streetwalking, driving a bus, or some other ill-paid employment. However, celebrities felt they had received the highest accolade in showbusiness by being invited to appear in "an Ernest Wide play" as Ernie once mispronounced it during a show's introduction involving 'Vanilla' (Vanessa) Redgrave.