He is the son of Dr. Tomáš Holomek (1911-1988), the first Rom in Czechoslovakia ever to finish university studies, at the Charles University in Prague, Faculty of Law. During the Nazi Protectorate (1939–1945), Karel Holomek should have been transported together with his sister to a concentration camp. With the help of a Czech officer, their mother managed to save the children. Many of Holomek’s family were murdered in CC Auschwitz II-Birkenau. After Holomek finished military high school, he studied at the Military Technical Academy in Brno graduating as a mechanical engineer (1960). Until 1969, he served in the Czechoslovak army where he held different technical positions. His last posting was as an Assistant Lecturer with the rank of major at the Military Academy.
During the so-called “Prague Spring” (1st April 1968 – 20th August 1968), he was working for the Association of Gypsies-Roma (AGR) as director of one of the plants – Nevodrom (a blacksmith factory) – an economic and purpose-built body of the AGR. At the beginning of 1969, he was expelled from the Communist Party and released from the army service for resisting the Warsaw Pact invasion of 20th – 21st August 1968. In 1981, he was charged with subversion of the Republic. Holomek was forced to work as a freight transport driver and as a foreman at building sites until 1990.
At the beginning of 1990, Holomek was elected MP of the Czech National Council (one of the then three Parliamentary bodies of the CSR) for the period of three years; he founded a non-governmental organization, the Association of Roma in Moravia. In 1999, he started a fortnightly newspaper, Romano hangos, as its first editor-in-chief. He was the decisive in the establishment of the Museum of Romani Culture. For twenty-five years, he was a member of the Co-ordination Council of the Czech-German Fund for the Future, a member of governmental councils for human rights and for Romani matters. In 2010, he published his book Dávné vzpomínky (Distant Memories).
In 2002, Holomek received from president Václav Havel a Distinguished Service Medal. In 2007, he was awarded Prix Irene from the Tolerance and Civil Association Society. In 2014, Holomek received, from Karel Schwarzenberg the Ferdinand Dobrotivý award for his publication activities and in 2015, he was awarded the prize of the World Romani Festival Khamoro. On 27 July, 2017, the Czech National Television aired an episode of the National Elite Gallery (NEG) about Karel Holomek. He became the first Rom ever to appear in the NEG.