Relocating to Sydney around 1910, it was here he took on the stage name of Roy Rene (Rene after a famous French clown) and became one of the most well-known performers on the Sydney vaudeville circuit. From 1916, Rene performed as the character Mo with Nat Phillips in the comedy duo 'Stiffy and Mo'. The duo became renowned around Australia for their 'blue' humour. Mo was known for his distinctive black and white face make-up. The pair split in 1925 and were reunited briefly in 1927 but the following year parted for good.

Rene then established his own theatre revue company, Mo and his Merrymakers. In 1934, he starred in the film Strike me lucky, the title of which comes from one of his many catchphrases. Other catchphrases included 'Don't come the raw prawn with me' (to tell someone not to try and deceive you or misrepresent the situation) and 'Fair suck of the sav' (to indicate incredulity or to let someone know they are not giving others a fair go). In the 1940s Rene turned to radio. His radio show McCackie Mansions, which aired from 1947 and featured Rene as the character Mo McCackie, earned him a huge following. Roy Rene died on 22 November 1954.

In 2010 a statue of Mo was erected in Hindley Street, across the road from the former site of the Theatre Royal.