Brett Leake worked as a standup comic from 1983 until 1997 when he began working as a sit-down standup comic, which he currently still does.

In 1998, he began to work also as a motivational speaker adding to his standup act, personal stories and what have been called 'philosophic lecturettes', that address using humor as a problem-solving device, and as a means to get more out of life. He has performed at the Smithsonian, the Kennedy Center, and Wolftrap.

Leake has facioscapulohumeral muscular dystrophy. In 1991, he became the first disabled comic to appear on NBC's The Tonight Show about which Jay Leno said, "He broke up the whole room. People realized here's a man with a disability and he's not gonna' let it bother him."

Leake's other television appearances include Entertainment Tonight and the American Comedy Awards. In 2003, public broadcasting stations around the country began running his hour-long comedy special "Laughing Matters with Brett Leake."