Mellon was a long-time Democrat whose political views often conflicted with those of her husband. In 2004, she expressed interest in presidential candidate John Edwards because he reminded her of President Kennedy, but when she called his campaign office with an offer to help, her name was not recognized and the call went unreturned. She was an early financier of Edwards' 2008 Democratic primary run, offering an initial US$1 million commitment to his campaign, and eventually contributing more than $3.5 million to organizations supporting his candidacy.