At varying times during his career, he also served as Minister of Finance, Minister of Education, Minister of the Interior, Minister of Public Health and Deputy Prime Minister. He also served as Acting Prime Minister during the Second World War, during the absence of his friend, General Jan Smuts.
Hofmeyr was an outspoken opponent of the growing racial discrimination and antisemitism in South Africa , becoming more liberal as the governments of the 1930s and 1940s became more discriminatory. His attitude towards non-whites was the vanguard of liberal opinion at the time, and he was one of the few leaders who openly spoke out against injustice when he saw it.
Although his outspokenness made him unpopular in some circles in the government, it showed his inflexible adherence to principle.