Ferrer, now the world number 21, is ranked just five places above Tomic and had lost to the Australian on their previous two encounters.
Earlier, Frenchman Nicolas Mahut came from 1-4 down in the third set to outlast fellow countryman Stephane Robert 4-6, 6-3, 6-4 in a two-hour marathon.
Britain's Kyle Edmund saw off American qualifier Ernesto Escobedo in two tiebreak sets 7-6 (7/4), 7-6 (8/6), while seventh seeded Bulgarian Grigor Dimitrov cruised past US player Steve Johnson 6-2, 6-3.
In the women's draw, reigning French Open champion Garbine Muguruza also disappointed the Queensland fans when she saw off hometown hero Samantha Stosur in a two-hour 45 minute epic.
The fourth seeded Muguruza came back from a break down in the third set to outlast Stosur 7-5, 6-7 (2/7), 7-5.
Earlier, two time Grand Slam champion Svetlana Kuznetsova celebrated her 600th win on the WTA Tour when she downed American Louisa Chirico 6-2, 6-4 and will now play either US qualifier Bethanie Mattek-Sands or young Australian Destanee Aiava.
Sixth seed Elina Svitolina of Ukraine was an impressive 6-3, 6-3 winner over Puerto Rica's Rio Olympic gold medallist Monica Puig, while China's Zhang Shuai downed German Laura Siegemund 4-6, 7-6 (7/3), 6-3.
Copyright Agence France-Presse, 2017